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• 10x Genomics Single Cell Gene Expression for SA604X9XB02425

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA604 passage 9

  Dataset EGAD00001009159

• 10x Genomics Single Cell Gene Expression for SA610X3XB03802

  10x Genomics Single Cell Gene Expression for Triple negative breast cancer patient-derived xenograft SA610 passage 3

  Dataset EGAD00001009160

• RNA-sequencing of ex vivo exhausted human antigen-specific T cells

  Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. To explore new pathways for reinvigoration of anti-tumor immune functions, we developed a human ex vivo exhaustion model by repetitive antigenic stimulation of primary CD8 T cells. This results in T cells that resemble patient-derived T cells in tumors on a phenotypic and transcriptional level. Four human healhy donor CD8+ T cells were isolated, transduced with an NY-ESO-1 TCR lentivirus construct, stimulated in four different conditions (Trested, Ttumor, Tex, Teff) with T2 tumor cells and specific peptides over 12 days. Cells were then sorted for TCR Vbeta 13.1+ (NY-ESO-1 TCR) CD8+ CD3+ CD56- CD4- DAPI- cells. RNA-seq TruSeq libraries were generated from polyA-enriched mRNA isolated from the samples, and sequenced in paired-end mode (2x51bp) on 2 lanes of an Illumina NovaSeq 6000 flow-cell. FASTQ sequence files were generated with the Illumina RTA version 3.4.4 and Base-calling Version bcl2fastq-2.20.0.422.

  Dataset EGAD00001009754

• Oesophageal adenocarcinoma RNAseq from LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19)

  This dataset contains bulk transcriptomes from the inoperable cohorts of the LUD2015-005 study (NCT02735239, EudraCT 2015-005298-19). Transcriptomes were prepared from pre-treatment oesophageal tumour biopsies using a ribodepletion approach in order to assess both previously reported (e.g. PD-L1 expression) and novel predictive expression-based biomarkers for immunochemotherapy treatment in this setting. On-treatment and post-treatment biopsies were generated as well to characterize response to therapy, and samples were also prepared from paired normal GI tissues for a subset of patients. scRNA-seq based deconvolution was also applied to bulk transcriptomes in this study to estimate the cell composition of tumour biopsies and assess the link between the presence of specific cell types with immunochemotherapy outcomes.

  Dataset EGAD00001009399

• The scRNA dataset for TIGIT in MCL with CART

  We collected longitudinal samples from 15 patients with MCL at various clinical time points before and after CAT-T therapy brexucabtagene autoleucel (BA) infusion. The patients were grouped into three categories based on their clinical responses after BA treatment: 1) responsive (n = 9), 2) relapsed (n = 5), and 3) refractory (n = 1). All patients in category #1 and #2 had initially attained a complete response (CR) after BA therapy. The responsive group maintained CR with no relapse at the time of last follow up, while the relapsed group achieved initial CR but eventually relapsed. The 10x Chromium™ Single-Cell 5′ Reagent Kit v2 (PN-1000190, 10x GENOMICS) and Chromium Single-Cell Human TCR amplification Kit (PN-1000252, 10x GENOMICS) were used to perform single-cell separation, cDNA amplification, and library construction for gene expression and TCR repertoire following the manufacturer’s guidelines. Thirty-nine samples passed quality control and underwent single-cell transcriptome profiling with simultaneous single-cell T-cell receptor (TCR) repertoire analysis.

  Dataset EGAD00001010180

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): Identification of VUR genes by exome sequencing

  Primary vesicoureteric reflux (PVUR), or non-syndromic VUR, is the most common type of congenital anomaly of the kidney and the urinary tract (CAKUT). PVUR is the single most important risk factor for pyelonephritis and renal parenchymal scarring in the pediatric age group. Renal parenchymal scarring due to PVUR is referred to as reflux nephropathy and is a major cause of end stage kidney disease requiring dialysis and kidney transplantation in children. PVUR shows familial aggregation; however, the specific genetic cause(s) of PVUR is unknown despite a number of linkage studies. Reasons for this include: variable expression of the disease, difficulty with case ascertainment, genetic heterogeneity and lack of large pedigrees that can facilitate locus identification. We have ascertained a large 97 member PVUR kindred spanning five generations. We performed a genome-wide linkage study (GWLS) on this family and obtained a significant genome-wide LOD score of 3.3 on chromosome 6p. We performed exome sequencing on affected individuals in the family and identified mutations in tenascin XB (TNXB) as a cause of familial VUR. The proposed studies have the following specific objectives: a) to define the role of tenascin genes in the etiology of PVUR, and b) to identify new PVUR causative genes. Our specific aims are (1) To perform mutation analysis in TNXB and other tenascins in a cohort of 200 individuals with familial and sporadic PVUR and define genotype/phenotype correlations. (2) To perform sequential genome wide linkage studies (GWLS) and whole exome/targeted sequencing in families with PVUR. Impact on public health: Identification of PVUR genes may provide a novel non-invasive diagnostic tool for a subset of children with PVUR. Furthermore, this research will provide insights into the pathogenesis of PVUR and further elucidate the pathways involved in the development of the kidney and genitourinary tract. Future studies will define the role of the genes in the etiology of other malformations of the kidney and urinary tract and also seek to unravel the mechanisms by which the identified gene causes PVUR and other malformations of the kidney and the urinary tract.

  Study phs000778

• The Familial Intracranial Aneurysm Linkage Study (FIA)

  Our long-term objective is to identify susceptibility genes that are related to the formation of intracranial aneurysms (IA). Rupture of IAs occurs in 16,000 to 17,000 persons in the U.S. annually and nearly half of affected persons are dead within the first 30 days. An additional 6,000 to 7,000 persons with unruptured IAs are identified each year. Accumulated evidence indicates that a genetic component plays an important role in the development of IAs, but specific loci affecting the risk of IA have not been identified. The primary hypothesis of this study is that there are specific human chromosomal regions that are associated with an increased risk of IAs. Specific Aims of are: Recruitment of 400 (475) families with multiple individuals who have an IA through 23 (25) referral centers throughout North America, Australia, and New Zealand that represent 35 (40) recruitment sites. Ascertainment of interviews and blood samples from all affected family members as well as their first-degree relatives. White blood cells from living persons with an IA will be cryopreserved at Coriell Institute for Medical Research for future immortalization of cells lines as indicated. Identification of unruptured IAs by obtaining MRAs in selected asymptomatic siblings (of affected individuals). Completion of a 10 cM genome series in persons with IAs as well as the spouses and children of persons with an IA who are deceased. We will perform finer mapping of chromosomal regions with suggestive evidence of linkage in the genome screen. Performance of a nonparametric (allele sharing) linkage analysis, including relevant environmental factors such as smoking, to identify chromosomal regions linked to IA. Reconstruction of the genotypes of deceased affected family members will be performed. Identification of individuals who are genetically at high risk for the development of IAs would enable targeted and effective screening/prevention/treatment strategies to reduce the substantial mortality and morbidity associated with this devastating type of stroke. Only a multidisciplinary, collaborative effort to identify, accrue, and genotype FIA families will be successful in identifying sufficient high-risk families to characterize the genetic underpinnings of IA.

  Study phs000293

• Exome Sequencing of Statin-Induced Myopathy Cases

  Severe myopathic events occur in 0.1-0.5% of patients taking statins. Although genetic association studies have identified some possibly associated gene loci, these have not been reproducible in additional studies with independent patient cohorts. A more reasonable explanation for susceptibility to statin-induced myopathy is the presence of rare pathogenic variants in genes important for skeletal muscle structure and function. In support of this, we have previously reported an increased incidence of pathogenic variants in genes causing metabolic myopathies in patients with statin-induced myopathy (Vladutiu et al.,2006). We also reported a patient with statin myopathy who had an RYR1 variant known to be causative of malignant hyperthermia susceptibility (MHS) (Vladutiu et al., 2011). There are a number of genes associated with metabolic myopathies triggered by various factors such as extreme exercise, fasting, extremes in temperature, viral infection and exposure to volatile anesthetics. In addition, many of the genes causing congenital myopathies, myofibrillar myopathies and muscular dystrophies have overlapping phenotypes with these genes. We propose that statins act as an additional trigger inducing myopathic symptoms and many patients with severe statin-induced myopathy have causative genetic variants within similar genes associated with MHS and congenital myopathy. We have analyzed the resultant data using a disease model in which rare pathogenic variants, possibly within multiple genes, are causative of statin-induced myopathy. In this study, we have identified potentially causative genetic variants in greater than 50% of the statin-induced myopathy cases and in particular, rare and possibly pathogenic in the RYR1 and CACNA1S genes were present in 25% of the patient samples studied. Vladutiu, G. D., Simmons, Z., Isackson, P.J., Tarnopolsky, M., Peltier, W.L., Barboi, A.C., Sripathi, N., Wortmann, R.L., Phillips, P.S., (2006). "Genetic risk factors associated with lipid-lowering drug-induced myopathies." Muscle Nerve 34: 153-162. Vladutiu, G. D., Isackson, P.J., Kaufman, K., Harley, J.B., Cobb, B., Christopher-Stine, L., Wortmann, R.L, (2011). "Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies." Mol Genet Metab 104: 167-173.

  Study phs001342

• Center Common Disease Genomics [CCDG] - CVD - TAICHI

  The TaiChi consortium consists of 6 studies that collaborated initially in a large scale metabochip study, and became an ongoing consortium for studies of cardiometabolic disease in the Chinese population in Taiwan. The six studies included the following: 1) SAPPHIRe (Stanford-Asian Pacific Program in Hypertension and Insulin Resistance), a family based study established in 1995 with an initial goal of identifying major genetic loci underlying hypertension and insulin resistance in East Asian populations, with Taiwan subjects participating in the TaiChi consortium; 2) TCAGEN (Taiwan Coronary Artery Disease GENetic), a cohort study that the enrolled patients undergoing coronary angiography or percutaneous intervention at the National Taiwan University Hospital (NTUH) in the setting of either stable angina pectoris or prior myocardial infarction; 3) TACT (TAiwan Coronary and Transcatheter intervention), a cohort study enrolled patients with angina pectoris and objective documentation of myocardial ischemia who underwent diagnostic coronary angiography and/or revascularization any time after October 2000 at the National Taiwan University Hospital (NTUH) (similar to TCAGEN but recruitment was independent of TCAGEN); 4) Taiwan DRAGON (Taiwan Diabetes and RelAted Genetic COmplicatioN), a cohort study of Type 2 diabetes at Taichung Veterans General Hospital (Taichung VGH) in Taiwan, with participants including individuals with either newly diagnosed or established diabetes (subjects with hyperglycemia who did not meet diagnostic criteria for Type 2 DM were not included); 5) TCAD (Taichung CAD study), includes patients with a variety of cardiovascular diseases who received care at the Taichung Veterans General Hospital (Taichung VGH), i.e. specifically individuals who were hospitalized for diagnostic and interventional coronary angiography examinations and treatment; 6) TUDR (Taiwan US Diabetic Retinopathy) enrolled subjects with Type 2 diabetes who received care at Taichung Veteran General Hospital (Taichung VGH), and a small number of subjects from Taipei Tri-Service General Hospital (TSGH); TUDR subjects underwent a complete ophthalmic and fundus examination to carefully document the presence and extent of retinopathy. From these 6 studies, subjects were selected based on completeness of standard metabolic phenotyping and knowledge of cardiac disease status (early onset coronary disease), to undergo whole genome sequencing at the Broad.

  Study phs001487

• Investigation of Brain Nitrogen Metabolism in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1H MRS, DTI, and fMRI

  This is a case controlled, observational study. This project studies cognitive and motor dysfunction in adult and pediatric patients who are female carriers of ornithine transcarbamylase deficiency (OTCD) or are males with late onset presentation (outside of the newborn period) of OTCD, utilizing state of the art MRI (magnetic resonance imaging), a non-invasive technique. This project seeks to improve our understanding of the underlying neural mechanisms that contribute to metabolic, cognitive, sensory and motor abnormalities in urea cycle disorders, which although individually rare, collectively constitute a major cause of neonatal encephalopathy, leading to significant morbidity and mortality. As a result of this study, a greater understanding of the anatomic, cognitive, motor, and biochemical underpinnings of neurologic damage attributable to this metabolic disorder will be gained. Experimental approaches will combine sensory, cognitive and motor testing with structural, functional and molecular magnetic resonance imaging to study symptomatic and asymptomatic heterozygous female carriers of X-linked ornithine transcarbamylase deficiency (OTCD), and late onset hemizygous males. Participants to be included in the studies ranged from ages 7-60 years and were compared to an age-matched typically developed (TD) comparison group. For our research, we use anatomic MRI, functional Magnetic Resonance Imaging (fMRI), and magnetic resonance spectroscopy (MRS) to monitor brain activity. The technique of fMRI provides detailed maps of the brain areas underlying human mental activities. By using fMRI, we are able to observe how the brain is functioning while a person is performing a specific task, such as reading. We can not only observe differences in the structure of the brain, but can also measure differences in brain function and activity as well. This information will ultimately be used to provide a basis for designing more effective interventions and methods for early identification of learning disabilities in patients with OTCD and related disorders. We will also use MRS to study various brain chemicals such as glutamine using the non-invasive MRI imaging techniques.

  Study phs001296

• National Institutes of Health The Cancer Genome Atlas (TCGA)

  The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. TCGA is a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), which are both part of the National Institutes of Health, U.S. Department of Health and Human Services. TCGA projects are organized by cancer type or subtype. Click here for a current list of cancer types selected for study in TCGA. Data from TCGA (e.g., gene expression, copy number variation and clinical information), are available via the Genomic Data Commons (GDC). Data from TCGA projects are organized into two tiers: Open Access and Controlled Access. Open Access data tier contains data that cannot be attributed to an individual research participant. The Open Access data tier does not require user certification. Data in Open Access tier are available in the TCGA Data Portal. Controlled Access data tier contains individual-level genotype data that are unique to an individual. Access to data in the Controlled Access data tier requires user certification through dbGaP Authorized Access. Controlled Access data types consist of the following: Individual germline variant data (SNP .cel files) Primary sequence data (.bam files), which are available at GDC Clinical free text fields Exon Array files (for Glioblastoma and Ovarian projects only) NOTE: TCGA strives to release most data in the open access tier. Individual genotype or sequence files are prominent exceptions. Commonly requested files such as descriptions of somatic mutations or clinical data are open access. Please go to this page: https://tcga-data.nci.nih.gov/docs/publications/ to access all data associated with TCGA tumor specific publications. The TCGA study is utilized in the following dbGaP substudies. To view genotypes and other molecular data collected in these substudies, please click on the following substudies below or in the "Substudies" section of this top-level study page phs000178 TCGA study. phs000854 Genome-wide Analysis of Noncoding Regulatory Mutations in Cancer

  Study phs000178

• Integrating Genomic and Transcriptomic Data to Identify Breast Cancer Susceptibility Genes

  Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. Since 2007, common genetic variants in ~200 loci have been identified in genome-wide association studies (GWAS) in relation to breast cancer risk. However, it is often difficult to translate GWAS findings to disease prevention and treatment since causal genes in the large majority of GWAS-identified loci are unknown. Furthermore, a large fraction of breast cancer heritability remains unexplained. Recent studies suggest that nearly 80% of disease heritability can be explained by genetic variants regulating gene expression. Herein, we propose three well-powered transcriptome-wide association studies (TWAS) to systematically investigate the association of breast cancer risk with gene expression across the transcriptome of African, Asian and European descendants. In Aim 1, we will perform RNA sequencing and high-density genotyping assays using normal breast tissue samples, and build race-specific gene expression prediction models using data from 1000 women of African, Asian and European descent. These models will be applied to the GWAS data generated from approximately 320,000 breast cancer patients and controls to impute gene expression for association analyses of predicted gene expression with risk of breast cancer overall, and by estrogen receptor and HER2 status. In Aim 2, we will select the top 50 genes identified in Aim 1 for in vitro functional assays to assess their influence on major cell functions related to cancer biology. In Aim 3, we will evaluate whether TWAS-identified genes may express differently in normal breast tissues and breast cancer tissues collected from African, Asian, and European descendants to assess whether these genes may contribute to racial differences in breast cancer risk by molecular subtypes. With strong methodology and a large sample size, we believe that this proposed study should be able to identify and characterize a large number of novel genes related to breast cancer risk. Uncovering breast cancer susceptibility genes will greatly improve the understanding of the genetic and biological basis for breast cancer and accelerate the translation of genetic findings to disease prevention and patient care.

  Study phs003535

• Contextual and Health Behavior Effects on Epigenetic Aging Among Africans in the Family and Community Health Studies

  The Family and Community Health Studies (FACHS) is a longitudinal examination of health and health related behaviors in African American families. The original study cohort consisted of 867 African American parent-child dyads from Georgia and Iowa who were ascertained in cooperation with local school districts. The key inclusion criteria for participating in the study were the presence of an adolescent in the 5th grade (approximately 10-11 years old) who self-identified as African American (i.e., the Target) and the participation of a primary caretaker (PC) for the Target. The clinical and biological data included in this collection are from the Target (i.e., FACHS-T) portion of these studies of these African American parent-child dyads. The initial wave of behavioral assessments of the FACHS-T subjects was conducted in 1997-98 (Wave 1), with seven subsequent ascertainments, Wave 2 (1999–2000), Wave 3 (2002–2003), Wave 4 (2005–2006), Wave 5 (2007–2009), Wave 6 (2010–2011), Wave 7 (2014–2016) and Wave 8 (2019-2021). Full interviews were obtained at each wave of the study with the exact content of the wave varying as a function of developmental age. These interviews of the FACHS-T subjects collected a wide variety of data including the following: perceived discrimination; socioeconomic status; substance use exposure; common internalizing and externalizing disorders such as depression, substance use, and conduct disorder; school efficacy; peer support and perceived parenting practices. Biological sampling of the FACHS-T subjects was conducted at three time points. Saliva DNA was collected at Wave 5 while full phlebotomy was conducted at Waves 7 and 8. The genome wide methylation data listed below is derived from the whole blood DNA samples collected at Wave 8 and Wave 9. The genome wide genotyping data was determined using DNA from the Wave 7 samples. The clinical and biological data available herein are those from 309 FACHS-T subjects who participated in both Wave 7 and Wave 8, and who consented for deposition of their data in dbGAP.

  Study phs003723

• NHLBI TOPMed: Lung Tissue Research Consortium (LTRC)

  Chronic obstructive pulmonary disease (COPD), a disease state characterized by airflow limitation that is not fully reversible, is the third leading cause of death in the U.S. COPD is a heterogeneous syndrome, with affected individuals demonstrating marked differences in lung structure (emphysema vs. airway disease); physiology (airflow obstruction); and other clinical features (e.g., exacerbations, co-morbid illnesses). Multiple genomic regions influencing COPD susceptibility have been identified by genome-wide association studies (GWAS), and rare coding variants can also influence risk for COPD. However, only a small percentage of the estimated heritability for COPD risk can be explained by known genetic loci. Like most complex diseases, COPD is influenced by multiple genetic determinants (each with modest individual effects). Emerging evidence supports the paradigm that complex disease genetic determinants are part of a network of interacting genes and proteins; perturbations of this network can increase disease risk. To identify this network, multiple Omics data will need to be analyzed with methods to account for nonlinear relationships and interactions between key genes and proteins. Our overall hypothesis is that integrated network analysis of genetic, transcriptomic, proteomic, and epigenetic data from biospecimens ranging from lung tissue to nasal epithelial cells to blood in highly phenotyped subjects will provide insights into COPD pathogenesis and heterogeneity. We will leverage the well-phenotyped, NHLBI-funded Lung Tissue Research Consortium (LTRC) to address these questions. We will perform multi-omics analysis in 1548 lung tissue and blood samples from the LTRC. With these multi-omics data, we will utilize a systems biology approach to understand relationships between multiple genetic determinants and multiple types of Omics data. We will begin by performing single Omics analyses in COPD vs. control lung, nasal, and blood samples. Next, we will integrate single Omics data with genetic variants identified by WGS to assist in fine mapping genetic determinants of COPD. We will then perform integrated network analysis of COPD with genetic and multiple Omics data using correlation-based, gene regulatory, and Bayesian networks. Subjects were recruited from Mayo Clinic, Universities of Colorado, Michigan, and Pittsburgh, and Temple University.

  Study phs001662

• METSIM (METabolic Syndrome In Men) Study

  The METSIM Study includes 10,197 men, aged from 45 to 73 years, randomly selected from the population register of the town of Kuopio, Eastern Finland, and examined in 2005-2010. The aim of the study is to investigate genetic and non-genetic factors associated with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), and insulin resistance-related traits in a cross-sectional and longitudinal setting. Study protocol includes collection of data on CVD risk factors (smoking, exercise, diet, history of chronic diseases including coronary heart disease, stroke, cardiac failure, medication, history of diabetes or early onset coronary heart disease in the family), questionnaire on the FINDRISC Score, measurement of height, weight, waist, hip, blood pressure, and bioimpedance for the evaluation of fat percentage. July 2016 - The first study release (v1) included phenotype and whole exome sequencing (WES) data of n=982 participants in substudy: Type 2 Diabetes Genetic Exploration by Next-Generation Sequencing in Multi-Ethnic Samples (T2D-GENES) Project 1: Metabolic Syndrome in Men Study (METSIM) - phs001100.v2.p1. The second study release (v2) included phenotype data for the entire METSIM cohort and made two additional substudies available, phs000919.v1.p1 and phs000752.v1.p1. The third study release (v3) made three subcutaneous adipose biopsy substudies available, phs003385.v1.p1, phs003386.v1.p1, and phs003387.v1.p1.The fourth study release (v4) added phenotype data for the subcutaneous adipose biopsies, made two additional substudies available, phs01579.v1.p1 and phs004033.v1.p1, and is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" section of this top-level study page phs000743 METSIM Study. phs000752 METSIM FinMetSeq Exome Sequencing phs000919 METSIM GWAS and Exome Chip phs001100 METSIM T2D-GENES Exome Sequencingphs001579 METSIM CCDG Whole Genome Sequencingphs003385 METSIM Subcutaneous Adipose Needle Biopsy RNA-Seq phs003386 METSIM Subcutaneous Adipose Needle Biopsy ATAC-Seq phs003387 METSIM Subcutaneous Adipose Surgical Biopsy RNA-Seqphs004033 METSIM Metabolomics

  Study phs000743

• Upcycling and merging data to challenge the dogma and identify new therapeutic targets for Glioblastoma

  Glioblastoma is the most common brain tumour. Characterised by a poor prognosis and its recurrence after multimodal treatments, the search for preventable risk factors has been mainly inconclusive up to date. Recently, the data merge from datasetsdeposited at the EGA allowed Aaron Diaz’s team to discover that the glioblastoma cells shift toward a mesenchymal phenotype when the tumour is recurring. Challenges in glioblastoma research As for virtually all cancer types, many efforts have been made to unveil the molecular features responsible of the disease, and several cellular pathways have indeed been identified as being frequently mutated in glioblastoma. Nonetheless, targeted therapies based on identified genes have so far failed to improve outcome, thus survival mostly relies on a standard treatment unchanged since 2005. This is a frustrating situation for both the scientific and medical communities, and above all for the patients, still facing a dreadful path. Some researchers hypothesised that this may be due to the inability to efficiently target cancer stem cells, the originators of the other cell types, thus inducing cancer relapse. In 2019 Charles P. Couturier and colleagues sequenced RNA from single cells of freshly excised glioblastomas of 16 patients, and demonstrated that glioblastoma cells replicate normal brain cell development with a conserved neural cancer cell hierarchy centered around glial progenitor-like cells. In this way, they helped identify the possible target cells to improve efficacy and durability of treatment. Data upcycling at the EGA: the glioblastoma case study Single cell RNA sequencing is generated with a laborious and expensive protocol. The quality of the starting material is crucial (cells sample freshly extracted from the patients) and often several attempts are needed before producing reliable quality sequencing results. Collecting big numbers of patients is also challenging. The sequencing data produced by Kevin Petrecca’s group in Montreal, Canada and deposited at the EGA (EGAS00001004422) was recently upcycled by Lin Wang in San Francisco, California and pooled with their freshly produced ones, and then deposited at the EGA as Dataset EGAS00001004909 The data merge allowed Aaron Diaz’s team to discover that the glioblastoma cells shift toward a mesenchymal phenotype when the tumour is recurring. They profiled 86 primary-recurrent patient-matched paired glioblastoma samples with single-nucleus RNA, among other techniques. These very comprehensive results lead the team to challenge the findings from several other cancer fields where chemotherapy standard chemo-radiation therapy selection pressure at the level of genomic alterations; this is indeed not the case for glioblastoma, where the pressure results in phenotypic transition between cellular states. Several technical controls were made to ensure that the merge of the data was not introducing a bias in the results, and an Inter-table analysis demonstrated nearly equal contribution to overall variance from each of the studies included, indicating that the findings were not due to inter-laboratory technical effect. A novel principal-component analysis showed that the largest contribution to variation in primary glioblastoma neoplastic cells was an axis between MES (mesenchymal) and proneural expression programs. In summary, treating glioblastoma often makes a MES, as commented by Lucy Stead about this remarkable work. Check Aaron Diaz’s team Nature Cancer paper, with strong technical tools, state of the art analysis and data from different sources converging to the same outcomes that made possible a significant step toward a better handling of a frightful cancer. References Couturier, C.P., Ayyadhury, S., Le, P.U. et al. Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy. Nat Commun 11, 3406 (2020). Stead, L.F. Treating glioblastoma often makes a MES. Nat Cancer 3, 1446–1448 (2022). Wang, L., Jung, J., Babikir, H. et al. A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets. Nat Cancer 3, 1534–1552 (2022). Related links: Kevin Petrecca’s group dataset deposited at the EGA: EGAS00001004422 Lin Wang dataset deposited at the EGA: EGAS00001004909

  Blog upcycling-and-merging-data-to-challenge-glioblastoma

• Scottish High Grade Serous Ovarian Cancer

  Scottish HGSOC samples were collected via local Bioresource facilities at Edinburgh, Glasgow, Dundee and Aberdeen and stored in liquid Nitrogen until required. HGSOC patients were determined from pathology records and were included in the study where there was matched tumour and whole blood samples. On receipt of tumour material the tumour was processed as follows: firstly, the tumour sample was divided into two for DNA and RNA extraction. Slivers of tissue were cut from the front and rear faces of the DNA sample, then fixed in formalin and embedded in paraffin wax. Sections from the front and rear tissues from all samples were examined by H&E staining supplemented by WT1/p53 immunohistochemistry if required. Following pathology review, samples were only included if they met the following criteria: they were confirmed as HGSOC and there was greater than 40% tumour cellularity throughout the tumour, determined using the H&E sections. Somatic DNA was extracted using the Qiagen DNeasy Blood and tissue kit (cat no 69504). The tissue was initially homogenised using a Qiagen Bioruptor, followed by the manufacturers recommended protocol (including RNase digestion step). Germline DNA was extracted from 1-3ml whole blood using the Qiagen FlexiGene kit (cat no 51206) following the manufacturers recommended protocol. The resulting DNA underwent quality control as follows: firstly, A260 and A280nm were measured on a Denovix DS-11 Fx to qualitatively illustrate A260/280nm and A260/230nm ratios as surrogate measures of DNA purity. A260/280 had to be 1.8 or greater and A260/230 had to be 2.0 or greater. Then, DNA was quantified using LifeTechnologies Qubit dsDNA BR kit (cat no Q32850) and we required a minimum of 50ul at 25ng/ul for WGS. Thirdly, DNA was diluted to 25ng/ul and a representative sample was loaded onto a 0.8% TAE gel, ran at 100v for 60mins and then imaged using a BioRad ChemiDoc imaging system to visualise the DNA quality. Only when all 4 quality control requirements were satisfied was the DNA sequenced. The DNA was sequenced at the Glasgow Precision Oncology Laboratories.

  Study EGAS00001004410

• Evolution and clinical impact of genetic epistasis within EGFR-mutant lung cancers

  The current understanding of tumorigenesis is largely centered on a monogenic driver oncogene model. This paradigm is incompatible with the prevailing clinical experience in most solid malignancies: monotherapy with a drug directed against an individual oncogenic driver typically results in incomplete clinical responses and eventual tumor progression1-7. By profiling the somatic genetic alterations present in over 2,000 cases of lung cancer, the leading cause of cancer mortality worldwide, we show that combinations of functional genetic alterations, i.e. genetic collectives dominate the landscape of advanced-stage disease. We highlight this polygenic landscape and evolution of advanced-stage non-small cell lung cancer (NSCLC) through the spatial-temporal genomic profiling of 7 distinct tumor biopsy specimens and 6 plasma specimens obtained from an EGFR-mutant NSCLC patient at (1) initial diagnosis of early-stage disease, (2) metastatic progression, (3) sequential treatment and resistance to 2 EGFR inhibitors, (4) death. The comprehensive genomic analysis of this case, coupled with circulating free (cf) tumor DNA profiling of additional advanced-stage EGFR-mutant NSCLC clinical cohorts with associated treatment responses uncovered features of evolutionary selection for multiple concurrent gene alterations: including the presence of EGFR inhibitor-sensitive (EGFRL858R;EGFRexon19del) or inhibitor-resistant (EGFRT790M;EGFRC797S) forms of oncogenic EGFR along with cell cycle gene alterations (e.g. in CDK4/6, CCNE1, RB1) and activating alterations in WNT/β-catenin and PI3K pathway genes, which our data suggest can cooperatively impart non-redundant functions to limit EGFR targeted therapy response and/or promote tumor progression. Moreover, evidence of an unanticipated parallel evolution of both EGFR T790M and two distinct forms of oncogenic PIK3CA was observed. Our study provides a large-scale clinical and genetic dataset of advanced-stage EGFR-mutant NSCLC, a rationale for specific polytherapy strategies such as EGFR and CDK4/6 inhibitor co-treatment to potentially enhance clinical outcomes, and prompts a re-evaluation of the prevailing paradigm of monogenic-based molecular stratification for targeted therapy. Instead, our findings highlight an alternative model of genetic collectives that operate through epistasis to drive lung cancer progression and therapy resistance.

  Study EGAS00001002604

• Identifying transcriptional programs underlying anti-EGFR small molecule response and resistance with TraCe-seq

  Genetic and non-genetic heterogeneity within cancer cell populations represents a major challenge to anti-cancer therapies. We currently lack robust methods to determine how pre-existing and adaptive features affect cellular responses to therapies. Here, by conducting clonal fitness mapping and transcriptional characterization using expressed barcodes and single-cell RNA-sequencing, we have developed TraCe-seq, a method that captures at clonal resolution the origin, fate, and differential early adaptive transcriptional programs of cells in a complex population in response to distinct treatments. We used TraCe-seq to benchmark how next-generation dual EGFR inhibitors-degraders compare to standard EGFR kinase inhibitors in EGFR-mutant lung cancer cells. To QC the TraCe-seq strategy, single-cell RNA-seq libraries were generated from a variety of human cancer cell lines transduced with the TraCe-seq library to validate the TraCe-seq strategy. Specifically, 5 different cell lines (PC9, MCF-10A, MDA-MB-231, NCI-H358, and NCI-H1373) were each transduced with a unique TraCe-seq barcode. The transduced cells were selected with puromycin only, dissociated to single cell suspensions, and then mixed together. The complex mixture of the 5 cell lines was profiled by 10X scRNA-seq. Furthermore, transduced NCI-H1373 cells were sorted by FACS to enrich for the top 50% of eGFP positive cells, and sorted cells were cultured briefly and used to construct scRNA-seq libraries and profiled by 10x scRNA-seq. To carry out the full TraCe-seq experiment, ~600 PC9 cells carrying unique TraCe-seq barcodes were expanded over 12 doublings to establish the barcoded population. A subset of the barcoded PC9 population was used to generate scRNA-seq libraries and profiled by 10x scRNA-seq prior to treatment to establish a baseline transcription profile for each barcoded clone. The rest of the cells were then treated for four days with 1 µM erlotinib, 1 µM GNE-069, or 1 µM GNE-104 respectively. scRNA-seq libraries were then generated form the treated cells and profiled by 10x scRNA-seq.

  Study EGAS00001005405

• Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets

  Untreated prostate cancers rely on androgen receptor (AR) signaling for growth and survival, forming the basis for the initial efficacy of androgen deprivation therapy (ADT). Yet, the disease can relapse and progress to a lethal stage termed castration-resistant prostate cancer (CRPC). Reactivation of AR signaling represents the most common driver of CRPC growth and next generation AR signaling inhibitors (ARSIs) are now used in combination with ADT as a first line therapy. However, ARSIs can result in selective pressure generating AR-independent tumors. The transition from AR-dependence frequently accompanies a change in phenotype resembling developmental trans-differentiation or ‘lineage plasticity’. Neuroendocrine prostate cancer, which lacks a defined pathologic classification, is the most studied type of lineage plasticity. However, most AR-null tumors do not exhibit neuroendocrine features and are classified as ‘double-negative prostate cancer’, the drivers of which are poorly defined. Lineage plasticity studies in CRPC are limited by the lack of genetically defined patient-derived models that recapitulate the disease spectrum. To address this, we developed a biobank of organoids generated from patient biopsies to study the landscape of metastatic CRPC and allow for functional validation assays. Proteins called transcription factors (TFs) are drivers of tumor lineage plasticity. To identify the key TFs that drive the growth of AR-independent tumors, we integrated epigenetic and transcriptomic data generated from CRPC models. By presenting a map of the chromatin accessibility and transcriptomic landscape of CRPC using a diverse biobank of organoids, PDXs and cell lines that recapitulate the heterogeneity of metastatic prostate cancer, we validate CRPC-AR and CRPC-NE subtypes and reveal two subtypes of AR-negative/low samples as well as their respective masterTFs. Additional analysis revealed a model in which YAP, TAZ, TEAD and AP-1 function together and drive oncogenic growth in CRPC-SCL samples. Overall, we show here how an approach to stratify CRPC patients into four subtypes using their transcriptomic signatures can potentially inform upon appropriate clinical decisions.

  Study EGAS00001006059

• Heart Failure Network: Functional Impact of GLP-1 for Heart Failure Treatment (HFN FIGHT-BioLINCC)

  Objectives To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. Background Heart failure was the leading cause of hospitalization in the United States with more than 4 million admissions per year from 2003–2009. Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). As heart failure progresses, these abnormalities become more pronounced and are observed in both patients with and without type 2 diabetes. At this time of this study, there was no heart failure therapy that targeted these metabolic abnormalities; however, in earlier clinical studies, glucagon-like peptide 1 (GLP-1) agonists showed cardioprotective effects in patients with advanced heart failure, irrespective of type 2 diabetes status. Glucagon-like peptide 1 is an endogenous incretin hormone that improves insulin sensitivity with minimal risk of hypoglycemia. This study was created to determine if use of GLP-1 agonists improved clinical stability in recently hospitalized patients with acute heart failure and reduced LVEF. Participants There were 300 participants. Design Participants were identified by hospital admission records and were enrolled during either the last 24 hours of his or her hospitalization for heart failure or the 2-week interval after the hospitalization. Baseline evaluations were conducted, which included echocardiographic measures, the 6-minute walk test, the Kansas City Cardiomyopathy Questionnaire (KCCQ), and blood tests. After the baseline evaluation, patients were randomized in a 1:1 ratio to receive either the GLP-1 agonist liraglutide or placebo as a daily subcutaneous injection. The protocol involved titration of study drug dosage as tolerated every 14 days from 0.6 mg/d to 1.2 mg/d to 1.8 mg/d during the first 30 days of the trial (as tolerated). Follow-up testing was performed at 30-, 90-, and 180-day study visits. The primary end point was a global rank score in which all participants, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level from baseline to 180 days. Conclusions The GLP-1 agonist liraglutide did not improve post-hospitalization clinical stability in patients with advanced heart failure and reduced LVEF. There was no significant between-group difference in the global rank scores and furthermore, there were no significant differences detected in any of the secondary endpoints.

  Study phs003542

• National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) Consortium Glaucoma Genome-Wide Association Study: Whole Exome Resequencing in Glaucoma

  This is a study of primary open angle glaucoma (POAG) conducted through exome sequencing of cases and comparison of variant frequencies with general population frequencies available in dbGAP and controlled for sequencing platform artifact to minimize false positives. POAG is an intraocular pressure (IOP) related progressive optic neuropathy that ultimately leads to blindness. This study builds upon the efforts of an on-going collaborative consortium that studied 2,170 POAG cases and 2,347 controls with a unified definition of POAG (the NEIGHBOR consortium: NEI Glaucoma Human genetic collaBORation). The case definition for NEIGHBOR was harmonized with an additional 976 cases and 1140 controls from the NHGRI supported GENEVA (gene-environment) study of glaucoma (GLAUGEN) (NIH/NHGRI U01HG004728, Pasquale PI). In NEIGHBOR, cases and controls were recruited from ophthalmology clinics and were examined by ophthalmologists. For cases, the clinical exam included intraocular pressure measurements, optic nerve assessment and visual field evaluation. Controls had no family history of glaucoma, normal intraocular pressure and normal optic nerves. Cases and controls were also drawn from two clinical trial populations: Advanced Glaucoma Intervention Study (AGIS, NEI U10EY006827, D. Gaasterland PI) and Collaborative Initial Glaucoma Treatment Study (CIGTS, NEI U10 EY009149, P. Lichter PI). The Glaucoma Exome Sequencing study has one Principal Investigator: Theresa Gaasterland (UCSD) and two Co-Investigators: Robert Weinreb, MD, and Kang Zhang, MD, PhD, all of whom are part of the NEIGHBOR, subsequently NEIGHBORHOOD, consortium, which in turn has two Co-Principal Investigators: J. Wiggs (Harvard, MEEI), and M. Hauser (Duke). NEIGHBOR collaborators who contributed samples and/or expertise to the Glaucoma Exome Sequencing study included the following: Harvard Medical School (Massachusetts Eye and Ear Infirmary) (J. Wiggs, L. Pasquale); Duke University Medical Center (M. Hauser, E. Hauser, R. Allingham, S. Schmidt); University of Michigan (J. Richards, S. Moroi, P. Lichter); University of Miami (M. Pericak-Vance, R. Lee, D. Budenz); Vanderbilt University (J. Haines); University of California San Diego (K. Zhang, R. Weinreb; T. Gaasterland); University of Pittsburgh (J. Schuman, G. Wollenstein); University of West Virginia (A. Realini, J. Charlton, S. Zareparsi); Johns Hopkins University (D. Friedman); Stanford University (D. Vollrath, K. Singh), Eye Doctors of Washington (D. Gaasterland), Marshfield Clinic (Cathy McCarty). Hemin Chin serves as the NEI Staff Collaborator. This national collaborative study is supported by multiple NIH grants: NEI R01 EY015543 (Allingham); NEI U10 EY006827 (D. Gaasterland); NHLBI R01 HL073389 (E. Hauser); NEI R01 EY13315 (M. Hauser); NEI U10 EY009149 (Lichter); NEI R01 EY015473 (Pasquale); NEI U10 EY012118 (Pericak-Vance); NEI R03 EY015682 (Realini); NEI R01 EY011671 (Richards); NEI R01 EY09580 (Richards); NEI R01 EY013178 (Schuman); NEI R01 EY015872 (Wiggs); NEI R01 EY009847 (Wiggs); NEI R01 EY010886 (Wiggs); NEI R01 EY144428 (Zhang); NEI R01 EY144448 (Zhang); NEI R01 EY18660 (Zhang). Funding support for genotyping through exome sequencing, which was performed at the University of California, San Diego, was provided by the National Eye Institute (RC2 EY020678-01).

  Study phs000558

• Population Architecture using Genomics and Epidemiology (PAGE)

  PAGE II (2013-2017) seeks to expand understanding gained during PAGE I and similar studies of how ancestry-specific differences in allele frequencies and LD may explain differences in risks of common traits and conditions. Recent studies have identified rare genetic variants that are likely to contribute to common diseases and traits and observed that rare variants likely to be functional, such as those in coding and regulatory regions, tend to be population-specific. PAGE II has genotyped over 50,000 samples using MEGA, an Illumina high density custom exomechip array. The MEGA data is being imputed in PAGE to the 1000 Genomes panel. PAGE also sequenced 1,000 samples representative of 21 populations from the Americas. PAGE has harmonized phenotype data for ~300 trait variables. These datasets will be analyzed to continue emphasis on characterizing population-level disease risks in non-European-descent individuals. Cohorts in PAGE II are: CALiCo (Causal Variants Across the Life Course, a consortium of ARIC, CARDIA, HCHS/SOL, Strong Heart Studies), ISMMS (Mount Sinai BioMe Biobank), MEC (Multiethnic Cohort), WHI (Women's Health Initiative), and Stanford University (PAGE Global Reference Panel). Genotyping services were provided by the Center for Inherited Disease Research (CIDR) and sequence data were provided by the McDonnell Genome Institute at Washington University School of Medicine. PAGE I (2008-2013): The first phase of PAGE examined putative causal genetic variants across approximately 100,000 African Americans, Asian Americans, American Indians, European Americans, Hispanic Americans, and Native Hawaiians from four groups representing nine large U.S.-based cohorts. Two genotyping approaches were employed - targeted genotyping of selected SNPs identified in genome-wide association studies of common disease, and a large-scale effort focused on the Metabochip array, which facilitated trans-ethnic fine mapping of several diseases of public health importance. Cohorts in PAGE I were: CALiCo (Causal Variants Across the Life Course, a consortium of ARIC, CARDIA, CHS, HCHS/SOL, Strong Heart Cohort Study, Strong Heart Family Study), EAGLE (Epidemiologic Architecture for Genes Linked to Environment, based on 3 National Health and Nutrition Examination Surveys (NHANES)), MEC (Multiethnic Cohort) and WHI (Women's Health Initiative). Logistical and scientific support is provided by the PAGE Coordinating Center and the NHGRI Division of Genomic Medicine. PAGE II is funded by the NHGRI and the NIMHD. To access PAGE studies currently available in dbGaP, please click on the links below.Please note that some PAGE studies belong to larger cohorts and have been included as PAGE substudies. For those studies, there is an additional link to the parent study. phs000223 PAGE-ARIC and phs000280 ARIC Cohort phs000236 PAGE-CARDIA and phs000285 CARDIA Cohort phs000301 PAGE-CHS and phs000287 CHS Cohort phs000559 PAGE-EAGLE-BioVu phs000208 PAGE-EAGLE-NHANES phs000555 PAGE-HCHS/SOL and phs000810 HCHS/SOL Cohort phs000220 PAGE-MEC phs000580 PAGE-SHS and SHFS phs001033 PAGE Global Reference Panel phs000227 PAGE-WHI and phs000200 WHI Cohort

  Study phs000356

• Heart Failure Network: Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF (HFN INDIE-BioLINCC)

  Data Access NOTEPlease refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.ObjectiveTo determine the effect of inhaled, nebulized inorganic nitrite on exercise capacity in patients with heart failure with preserved ejection fraction. Background Approximately half of patients with heart failure have a preserved ejection fraction (HFpEF). However, there are no proven effective medical treatments for this syndrome. Evidence suggests that impairments in nitric oxide availability have a potentially important role in the pathophysiology of HFpEF. Unlike organic nitrates, inorganic nitrite is converted to nitric oxide in the presence of hypoxia and acidosis, conditions that develop during exercise. Because the cardiac, vascular, and skeletal muscle abnormalities that limit physical capacity and contribute to symptoms in patients with HFpEF characteristically develop during exercise, inorganic nitrite may provide the best way to target nitric oxide delivery precisely at the time of greatest need. The HFN-INDIE trial was initiated to test the hypothesis that compared to placebo, longer-term use of inhaled, nebulized inorganic nitrite would enhance peak exercise capacity in patients with HFpEF. Participants A total of 105 participants were randomized. 53 were randomized to receive nitrite first and 52 were randomized to receive placebo first. Design HFN-INDIE was a multicenter, randomized, double-blind, placebo-controlled, crossover study. After enrollment, patients underwent baseline studies to determine eligibility. All patients were required to display objective exercise limitation, evidenced by reduced peak oxygen consumption (V̇O2) on cardiopulmonary exercise testing of less than 75% predicted, with a respiratory exchange ratio indicative of maximal effort (≥1.0). Following qualifying exercise testing, eligible participants received an open-label, single-dose run-in of inhaled, nebulized sodium nitrite (80 mg) to assess tolerability, symptoms, and orthostatic vital signs. Patients developing hypotension (systolic blood pressure The prespecified primary end point was peak V̇o2, measured as the highest 30-second average during upright cycle ergometry, during the 4-week period in which patients were receiving inorganic nitrite as compared with placebo. Accelerometry, health-related quality-of-life scores on the self-administered Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores indicating better quality of life), echocardiographic indicators of cardiac filling pressures measured at trough drug levels (E/e' ratio, estimated pulmonary artery systolic pressure, and left atrial volume index; lower scores indicate better health for all), ventilatory efficiency (VE/V̇co2, lower indicating better health), exercise time (higher indicating better health), and NT-proBNP levels (lower indicating better health) were also collected. Conclusions Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity. Borlaug et al., 2018, PMID: 30398602.

  Study phs003667

• The Finland-United States Investigation of NIDDM Genetics (FUSION) Study - Islet Expression and Regulation by RNAseq and ATACseq

  This study evaluates gene expression and its regulation in human pancreatic islets, a tissue relevant in the study of genetic risk factors contributing to diabetes. We obtained pancreatic tissue sections and purified pancreatic islets from deceased donors and processed these biological samples to generate various data types. We generated spatial transcriptomic data from pancreatic tissue samples using the 10X Genomics VISIUM technology with sequencing on the Illumina NovaSeq platform. We also generated multiple data types from the purified pancreatic islets using genome-wide SNP chips, bulk RNA-Seq, microRNA (miRNA)-Seq, whole genome sequence, DNA methylation (methyl)-Seq, cap analysis of gene expression (CAGE)-Seq, single cell RNA-seq, and single nuclei ATAC-seq approaches. These data include ATAC-seq of two islet subjects, RNA-seq of 31 additional subjects, genome-wide chip genotypes, and imputed genotypes of the 33 subjects released with phs001188.v1. For genotyping, 500-1000 islet equivalents (IEQ) were cultured as in Gershengorn (Science, 2004, PMID: 15564314); genomic DNA isolated from islet cultures. For RNA analyses, 2500-5000 IEQ from each islet source were used for bulk or single-cell RNA isolation. Messenger RNA was isolated with trizol extraction and 12-plex libraries were generated using the Illumina TruSeq directional mRNA-seq library protocol. Bulk RNA sequencing was performed on HiSeq2000/HiSeq2500/Hiseq4000/NovaSeq6000 sequencers using paired-end reads at the NIH Intramural Sequencing Center (NISC). miRNA libraries were prepared from total RNA from 68 samples, pooled and sequenced 50bp single-end reads on Illumina HiSeq2500. CAGE libraries were prepared from total RNA samples using the nAnT-iCAGE protocol at DNAFORM, Japan. CAGE libraries were sequenced at the NIH Intramural Sequencing Center (NISC) on the HiSeq2000 sequencer. Genotyping on the Illumina Omni2.5M array was performed at the NHGRI Genomics Core facility. Genotypes were imputed using the HRC.r1.1.2016 reference panel. To assess regions of open chromatin in islets, we performed bulk ATAC-seq on HiSeq2000 sequencers using paired-end reads at NISC. Single-nuclei ATAC-seq libraries were prepared using single-cell-combinatorial-indexing (sci-) ATAC-seq protocol and sequenced on Illumina NextSeq using paired-end reads. scRNA-seq libraries were generated using the 10X Genomics platform and sequenced on Illumina HiSeq3000 at the Genomics Technology Core of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Greater than 90% of the loci associated with T2D through genome-wide association studies occur in non-coding regions, suggesting a strong regulatory component to disease susceptibility. Therefore, there is a critical need to understand the full spectrum of genetic variation and regulatory element usage in T2D-relevant tissues. To that end, this study contains multiple genomic and transcriptomic data sets from pancreas tissue sections and pancreatic islets, a resource that will contribute to our efforts to investigate the genetic risk factors for type 2 diabetes.

  Study phs001188