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• Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS)

  GERFHS is a population-based, case-control study of hemorrhagic stroke in the Greater Cincinnati/Northern Kentucky region. Cases are recruited from within 50 miles of the University of Cincinnati and population-based controls are matched to cases by age (+/- 5 years), race and gender from the same population as cases. All study participants are of self-reported non-Hispanic Caucasian ethnicity and the data show consistency with the principal component projections. The current submission includes genome wide genotyping on a subset of these cases and controls.

  Study phs000874

• NHLBI TOPMed: Heart and Vascular Health Study (HVH)

  Objectives The Heart and Vascular Health Study (HVH) is a case-control study of risk factors for the development of myocardial infarction (MI), stroke, venous thrombosis (VT), and atrial fibrillation (AF). The study setting is Group Health, an integrated health care delivery system in Washington State. Only VT cases and early-onset AF cases are included as part of TOPMed. Background The HVH study originated in 1988 with the examination of risk factors for MI. Over the ensuing years, the study has been funded by a series of grants which have added case subjects with stroke, VT, and AF. Study aims focused on the associations of medication use with cardiovascular events, and starting in 1997, the study aims expanded to include genetic associations with cardiovascular disease. Participants recruited in 2009 or later who provided blood samples for genetic analysis were asked for consent to deposit genetic and phenotypic data in dbGaP. Design As part of the HVH study, case subjects were identified by searching for ICD-9 codes consistent with MI, stroke, VT, or AF, and medical records were reviewed to confirm the diagnosis. Control subjects were identified at random from the Group Health enrollment and were matched to MI cases. All subjects have an index date. For cases, the index date was assigned as the date that the cardiovascular event (MI, stroke, VT, or AF) came to clinical attention. For controls, the index date was a random date within the range of the case index dates. For both cases and controls, information was collected from the inpatient and outpatient medical record, by telephone interview with consenting survivors, and from the Group Health pharmacy and laboratory databases. Consenting participants provided a blood specimen. Subjects Only VT and early-onset AF cases from HVH are included in TOPMed. Within the HVH study, VT and AF cases were diagnosed in both inpatient and outpatient settings, and only incident cases are eligible for inclusion in TOPMed. Genetic Research Genetic factors underlying cardiovascular disease are studied using DNA isolated from the blood samples. Phenotype data for HVH study participants are available through dbGaP phs001013.

  Study phs000993

• Bladder Chemotherapy Responders

  Cisplatin-based chemotherapy is the standard of care for patients with muscle invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based chemotherapy is associated with improved survival, and some patients with metastatic disease achieve complete responses to these therapies. However, the molecular determinants of cisplatin response are incompletely understood. We performed whole exome sequencing on tumor and germline DNA from patients with muscle invasive or metastatic urothelial carcinoma who received cisplatin-based chemotherapy to identify somatic mutations that occurred preferentially in cisplatin responders.

  Study phs000771

• Center for Common Disease Genomics [CCDG] - Cardiovascular: Genetic and Phenotypic Determinants of Blood Pressure and Other Cardiovascular Risk Factors

  This study is a part of NHGRI's Center for Common Disease Genomics, which is a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Current estimates anticipate that the CCDG program will sequence approximately 140K whole genomes and 225K whole exomes during the life of the project. The Cardiovascular Disease working group of the CCDG considered five diseases: early-onset coronary artery disease (EOCAD), stroke, atrial fibrillation, congestive heart failure and type 2 diabetes. Atrial fibrillation will affect between 6-12 million individuals in the US by 2050. AF also is associated with increased risks of stroke, dementia, heart failure, death, and high health care costs. Many risk factors for AF have been identified, including advancing age, cardiovascular disease (CVD), and CVD risk factors. However, there is little knowledge how to prevent AF. Furthermore, therapies for AF are only partially effective, and are themselves associated with substantial morbidity. Previously, heritable forms of AF have been considered rare; yet in the last decade, it has been established that AF, and in particular early-onset forms of AF, are heritable. Genome-wide association studies (GWAS) provide a powerful tool to identify common variants underlying disease risk. The AFGen Consortium currently consists of investigators from more than 25 studies with >20,000 individuals with AF and >100,000 without AF. In the latest analyses, 14 loci have been identified for AF1. Broadly, the loci implicate genes related to cardiopulmonary development, cardiac-expressed ion channels, and cell signaling molecules. Source: ccdg.rutgers.edu The GAPP study is an ongoing national population-based prospective cohort study conducted in the Principality of Liechtenstein. Between 2010 and 2014, all inhabitants of Liechtenstein aged 25-41 years old were asked to participate in the study, and 2170 could be enrolled. The aim of the study is to identify the determinants of blood pressure and other cardiovascular risk factors and their progression over time. A large number of baseline characteristics and health information as well as several blood, urinary and genetic markers were collected. The samples were sent to The Broad Institute of MIT and Harvard to generate genetic data using whole exome sequencing and whole genome genotyping (Infinium Global Screening Array); all samples serving as controls.

  Study phs002236

• The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge

  Tumors are composed of many different cell types, ranging from the normal tissue micro-environment, infiltrating immune cells and tumour cells. This group of tumour cells is itself intrinsically highly heterogeneous, driven by the rapid mutation rate of cancer cells to become a mixture of different sub-populations. These different types of cells, called subclones, have different sets of mutations in their DNA. Because some subclones evolve from others, many subclones share mutations. While it is increasingly easy to determine what mutations are present in the tumor, it remains very difficult to determine which subclones have which mutations. The task of assigning mutations to subclones is called subclonal reconstruction.The ICGC-TCGA DREAM Somatic Mutation Calling - Tumour Heterogeneity Challenge (SMC-Het) is an international effort to improve standard methods for subclonal reconstruction: to quantify and genotype each individual cell population present within a tumor. The goal of this challenge is to identify the best subclonal reconstruction algorithms and to identify the conditions that affect their performance.

  Study EGAS00001002092

• AIDS Linked to the Intravenous Experience (ALIVE) Cohort

  The AIDS Linked to the Intravenous Experience (ALIVE) Study is a long-standing community based research effort that includes past and current injection drug users (IDUs). ALIVE has been ongoing since 1988 and is one of the longest-running community-based cohorts of IDUs in existence. The primary objectives when the study started were to characterize the incidence and natural history of HIV among injection drug users (IDUs). At each study visit, participants undergo a series of questionnaires that elicit information about substance use (including drugs used and route of administration) and a blood draw. A subsample of 1200 subjects was selected for genotyping for the NIDA Smokescreen effort who report heroin injection and have existing peripheral blood samples (isolated buffy coat). In addition to injected heroin, ALIVE subjects are assessed on lifetime and previous six months use of marijuana (76.3%), crack (55.5%), snorted cocaine (48.3%), injected cocaine (89.9%), injected speedball (87.0%), and smoking heroin (9.0%). The sample is 33.4% female, ~85% African-American and assessed through a mean maximum age of 49.9 years old. Importantly, subjects are not assessed to meet DSM criteria, but all subjects report having injected drugs. We provide demographic data (age at assessment, sex, self-reported race) and drug use data (lifetime "use" ever endorsed) for each drug class/route described above for each subject

  Study phs001494

• Center for Common Disease Genomics [CCDG] - Cardiovascular: The Genetics of Atrial Fibrillation

  This study is a part of NHGRI's Center for Common Disease Genomics, which is a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes. Current estimates anticipate that the CCDG program will sequence approximately 140K whole genomes and 225K whole exomes during the life of the project. The Cardiovascular Disease working group of the CCDG considered five diseases: early-onset coronary artery disease (EOCAD), stroke, atrial fibrillation, congestive heart failure and type 2 diabetes. Atrial fibrillation will affect between 6-12 million individuals in the US by 2050. AF also is associated with increased risks of stroke, dementia, heart failure, death, and high health care costs. Many risk factors for AF have been identified, including advancing age, cardiovascular disease (CVD), and CVD risk factors. However, there is little knowledge how to prevent AF. Furthermore, therapies for AF are only partially effective, and are themselves associated with substantial morbidity. Previously, heritable forms of AF have been considered rare; yet in the last decade, it has been established that AF, and in particular early-onset forms of AF, are heritable. Genome-wide association studies (GWAS) provide a powerful tool to identify common variants underlying disease risk. The AFGen Consortium currently consists of investigators from more than 25 studies with >20,000 individuals with AF and >100,000 without AF. In the latest analyses, 14 loci have been identified for AF1 . Broadly, the loci implicate genes related to cardiopulmonary development, cardiac-expressed ion channels, and cell signaling molecules.Source: https://ccdg.rutgers.edu/sites/default/files/CCDG_CVD_EOAF_FINAL_w_link.pdfFor this study, The Broad Institute of MIT and Harvard generated genetic data for UWO Genetic Investigation of Supraventricular Tachycardias.Patients confirmed to possess a supraventricular tachycardia and/or an accessory pathway at the time of invasive electrophysiology study at the London Health Sciences Centre, London, Ontario, Canada were eligible for enrollment. Potential supraventricular tachycardias included atrioventricular nodal reentrant tachycardia (AVNRT), atrioventricular reentrant tachycardia (AVRT), atrial tachycardia, junctional tachycardia, atriofascicular tachycardia, nodofascicular tachycardia, and nodoventricular tachycardia. Patients that did not have inducible supraventricular tachycardia, but had an accessory pathway that conducted antegrade, retrograde, or both, were also eligible for enrollment. All patients additionally underwent, at minimum, a clinical history, physical examination, 12-lead ECG, and echocardiogram. Study participants provided informed written consent under a protocol approved by the research ethics board of Western University.Raw sequencing data, metadata, vcf and phenotype data at individual level are available at https://anvilproject.org/data For questions about availability contact help@lists.anvilproject.org.

  Study phs002811

• Transcriptome sequencing of gingivo-buccal oral squamous cell carcinoma for integrative analysis: alterations in expression of genes attributable to methylation changes

  Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the most common cancer among men in India and is associated with high mortality. Although OSCC-GB is known to be quite different from tongue cancer in its genomic presentation and its clinical behavior, it is treated identically as tongue cancer. Predictive markers of prognosis and therapy that are specific to OSCC-GB are, therefore, required. To achieve this, we have carried out transcriptome (n=72) profiling of paired tumor-normal tissues collected from OSCC-GB patients from India. RNA sequencing was performed on tumor and paired adjacent normal samples from 72 OSCC-GB patients. From each patient, total RNA was extracted from tumor and normal tissue samples using AllPrep DNA/RNA Mini Kit (QIAGEN). The quality and concentration of isolated total RNA were checked using Agilent 2100 Bioanalyzer and NanoDrop 2000 (Thermo Fisher Scientific). The OD260/OD280 ratio was ≥ 2 and RNA Integrity Number (RIN) was ≥ 7.0 for all sequenced samples. Ribosomal RNA (rRNA) was removed from the RNA samples, using Ribo-Zero Magnetic Kit (Epicentre). Sequencing libraries were prepared from rRNA depleted samples using TrueSeq RNA Sample Preparation Kit (Illumina). Each triplex cDNA library pool was sequenced as 100bp paired-end on HiSeq-2000 or HiSeq-2500 (Illumina). Protocols suggested by the manufacturers were used for all assays.

  Study EGAS00001003893

• RNAseq dataset

  RNAseq experiment after DIS3 ASO or Control ASO treatment on human cells under plasmablast differentiation.

  Dataset EGAD50000001243

• Pancreatic adenocarcinoma QCMG 20110901

  Pancreatic adenocarcinoma QCMG 20110901

  Dataset EGAD00001000049

• Genome-wide DNA Methylation Data from Illumina HumanMethylationEPIC arrays for whole blood samples from 403 healthy individuals

  Genome-wide DNA Methylation Data from Illumina HumanMethylationEPIC arrays for whole blood samples from 403 healthy individuals. Additional associated phenotype information is available for all individuals included in this study directly from CIBMTR. Data are available under controlled access release upon reasonable request and execution of a data use agreement. Requests should be submitted to CIBMTR at info-request@mcw.edu and include the study reference IB17-04.

  Study EGAS00001006033

• Common origin and somatic mutation patterns of composite lymphomas and leukemias

  When two lymphomas occur concurrently or sequentially in a patient, it is a major question whether they derive from the same lymphocyte or hematopoietic precursor cell or developed independently. We studied four composite classic Hodgkin lymphomas (HL) and other mature B-cell lymphomas, and two composite mature B- and T-cell neoplasias by whole exome sequencing (WES) and analyzed shared somatic mutations in the lymphomas of these clonally related composite lymphomas, indicating their derivation from a common, pre-malignant precursor. Most identified mutations were restricted to one or the other of these lymphomas, likely explaining how distinct lymphomas developed from a common ancestral B cell. In the two B-cell/T-cell lymphoma cases, and a composite clonally unrelated HL/chronic lymphocytic leukemia, the lymphoma partners did not share any somatic mutations. In three cases, we identified potentially oncogenic variants also in cells serving as constitutional controls.

  Study EGAS50000001017

• Transcriptomics_of_human_olfactory_mucosa

  The olfactory gene repertoire is largely species-specific, shaped by the nature and necessityof chemosensory information for survival in each species' niche. We are intrigued by thisinterspecific variation and started to investigate the olfactory transcriptome in primates forevidence of selection at the level of receptor gene choice. Having collected this data fromtwo primates, we now wish to extend the analysis to humans.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001001486

• Pediatric Investigation of Genetic Factors Linked with Renal Progression (PediGFR): Chronic Kidney Disease in Children Cohort (CKiD)

  The Pediatric Investigation for Genetic Factors Associated with Renal Progression (PediGFR) (RO1-DK082394) is an international collaborative study among three large prospective cohort studies of children with chronic kidney disease. The participating parent cohort studies are the "Chronic Kidney Disease in Children (CKiD)", the "Effect of Strict Blood Pressure Control and ACE Inhibition on CRF Progression in Pediatric Patients (ESCAPE)", and the "Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C)" study. In these cohorts, pediatric subjects with CKD have been prospectively followed with standardized measurements for renal progression. The current version of the upload includes the genotype and baseline phenotype for the CKiD cohort. In brief the CKiD study is a prospective study of children with chronic kidney disease (CKD) between the ages of 1 year to 16 years of age and an estimated glomerular filtration rate (eGFR) by Schwartz equation between 30 and 75 ml/min per 1.73m2. Included in this upload are the phenotypic data for anemia traits utilized for the sub-study, "Role of Genetic Variation in the Anemia of Chronic Kidney Disease" (K24DK078737), with the RBC trait and anemia data pertaining to CKiD as well.

  Study phs000650

• GenomeDenmark Phase 2 - whole genome variants called using BayesTyper

  Variants and genotypes called in 50 danish parent-offspring trios from 80x Illumina sequencing data using BayesTyper. Data was produced using different insert size libraries of the sizes 180, 500, 800, 2000, 5000, 10000 and 20000 bp. The sample IDs for the fathers and mothers are TrioID-01 and TrioID-02, respectively, and the IDs for the children are TrioID-0x, where x is a number between 3 and 7

  Dataset EGAD00001003188

• Genomic Landscape of High-Grade Neuroendocrine Neoplasms

  This project is a multi-omics study of high grade (grade 3) neuroendocrine neoplasms across diverse organs. Genomic analysis using low-pass whole genome sequencing for copy number analysis, whole exome sequencing and whole transcriptomic sequencing using RNAseq were performed. As high grade neuroendocrine neoplasms are highly lethal with a median survival of approximately 7 months, new insights are urgently needed for better prognosis, diagnosis and management. This study focuses on gene and pathway discoveries in this cancer, and includes samples from a diverse set of organs, including the lungs, gastroenteropancreatic tract, breast, prostate, head and neck and bladder. This study was made possible by a generous donation from The Helen B. Rodde Fund.

  Study phs002070

• The International Consortium for Prostate Cancer Genetics Genome Wide Association Study of Familial Prostate Cancer

  Initially, the ICPCG focused largely on high-risk prostate cancer pedigrees using linkage analysis. However, association studies have also been informative to find prostate cancer susceptibility variants in the genome. We hypothesize that genome-wide (GW) association studies of familial cases of prostate cancer will have the power to identify rarer and perhaps less penetrant risk variants associated with prostate cancer than have been identified to date. Our approach will be to examine evidence for association in selected, independent cases from high-risk pedigrees; we hypothesize that they represent a more homogeneous set of cases with potentially different associations. Use of the 5M plus exome SNP platform will allow us to include in our search more rare variants in our search than have ever been investigated for prostate cancer. Aim 1. Identify a set of independent prostate cancer cases selected from ICPCG high-risk prostate cancer pedigrees that have 3 or more related prostate cancer cases and have an average age at diagnosis ≤ 75 years. Identify appropriate matched controls from participating ICPCG groups/ populations. Aim 2. Perform GW SNP genotyping with the Illumina 5M plus exome SNP set on the set of independent prostate cancer cases and controls described in Aim 1. Aim 3. Perform association analyses appropriately matching controls for different ICPCG populations and groups. There will be a two-stage design for confirmation. Aim 4. Test reported associations using the extensive sample set available to us by collaboration with the PRACTICAL consortium that has access to 50 000 DNA samples from 34 groups internationally (over 7,000 of whom are positive for prostate cancer family history).

  Study phs000733

• Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In Vivo

  Oncogenic alterations in EGFR frequently co-occur with additional genetic alterations in EGFR-driven lung adenocarcinoma (LUAD), but how specific combinations of mutations affect tumor phenotypes and responses to targeted therapy is yet unknown. We leveraged a genetically engineered mouse model of EGFR mutant/Trp53-deficient LUAD to study the consequences of inactivating 10 different tumor suppressor genes on the fitness and tyorosine kinase inhibitor (TKI) sensitivity of these tumors. We found that loss of Keap1 is associated with a reduced response to therapy. In patients, we found that mutations in the KEAP1/NFE2L2/CUL3 pathway are associated with a significantly shorter time to treatment failure for EGFR TKI therapy compared to matched patients with wild-type KEAP1/NFE2L2/CUL3 tumors. We also analyzed whole exome sequencing data from tumor specimens before TKI treatment and at the time of treatment resistance for mutations in the KEAP1 pathway and these data are being submitted here.  

  Study phs002334

• Molecular Characterization of Response to Rectal Chemoradiation

  Pre-operative chemoradiation (CRT) followed by resection is the standard of care option for patients with locally advanced rectal adenocarcinoma. Pathologic downstaging after CRT is associated with improved outcomes, but molecular predictors of response are poorly understood. We performed whole exome sequencing, gene expression profiling, and immune infiltrate analysis on rectal adenocarcinoma tumors prior to neoadjuvant CRT (pre-CRT) and at the time of resection (post-CRT) in 17 patients to identify somatic mutations and derive molecular biomarkers distinguishing complete and excellent partial responders versus non-responders.

  Study phs001829

• RNA-seq analysis of metastatic prostate cancer solid tumor biopsies

  The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)–targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study. Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival.

  Study EGAS00001006369

• Tam-seq of germline samples for HGSOC copy-number signatures study

  This dataset contains targeted amplicon sequencing of Germline DNA extracted from 56 blood samples. They were sequenced on Illumina HiSeq 2500 and aligned to human genome assembly GRCh37 (hg19)to produce 127 bam files (2-3 technical replicates per sample).

  Dataset EGAD00001004172

• Michigan Polybrominated Biphenyl (PBB) Exposure Registry

  Humans are exposed to chemicals such as brominated flame retardants (BFRs) at unprecedented levels, and a wide variety of health effects are attributed to such exposures. However, the biological mechanisms that link exposures to its consequences remain unknown. An industrial accident in the 1970's exposed over 4000 individuals in rural Michigan to polybrominated biphenyl (PBB), a BFR that was present in the food supply for years prior to detection and management. Health effects are still evident in these individuals and their children. Because this population has been assessed regularly since the exposure, it is an ideal group in which to examine the molecular mechanisms that contribute to susceptibility, vulnerability and health effects. The goal of this project is to identify the genetic variants that associate with the rate of PBB elimination over time and integrate genetic and epigenetic datasets and identify complex gene-environment relationships in PBB exposed individuals. We will leverage data generated as part of past and ongoing studies in the Michigan Polybrominated Biphenyl Registry. We anticipate that this study will provide insight into how genetic variants and the environment interact in relation to PBB exposure and its health effects. We also anticipate the results of this study will be informative for studies of BFRs and other endocrine disrupting compounds with similar chemical properties. Note that methylation array data is available from NCBI GEO under GSE116339: Exposure to Polybrominated Biphenyl (PBB) Associates with DNA Methylation Differences Across the Genome

  Study phs001862

• Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study - Maternal Glycemia and Birthweight GEI Study

  Low and high birth weight are not only major causes of neonatal morbidity and mortality, but epidemiological data have established an association between birth weight and later life risk of adult metabolic diseases. Fetal growth is determined by complex interactions between fetal genes and the maternal uterine environment. Subtle or overt variation in maternal glucose tolerance, which is, in part, genetically determined, is related to fetal size at birth. Moreover, new emerging data suggest that genetic variation in the fetus can impact maternal metabolism (e.g., blood pressure and glucose tolerance). Given the above, we are addressing the hypothesis that, during pregnancy, gene-environment interactions in the context of the maternal-fetal unit impact fetal size at birth and maternal metabolism. Genes that control fetal growth or maternal metabolism during pregnancy are largely unknown, so the first step to address our hypothesis will be to identify genetic variation that impacts fetal growth and maternal metabolism and to determine the interaction of that variation with the intrauterine and fetal environment. To accomplish this, we are performing genome wide association (GWA) mapping on a subset of ~37,000 DNA samples that were collected from mothers and their offspring as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. HAPO is a multicenter, international study in which high quality phenotypic data related to fetal growth and maternal glucose metabolism has been collected from 25,000 pregnant women of varied racial and socio-demographic backgrounds using standardized protocols that were uniform across centers. For these studies, we are genotyping 1,500 infants and their mothers of European descent, 1,250 Afro-Caribbean infants and mothers, 800 Hispanic (Mexican-American) infants and mothers, and 1200 Thai infants and mothers. Genotyping is being performed using the Illumina Human610 Quad (European ancestry participants), Human1M Duo (Afro-Caribbean and Hispanic participants), and Omni1-Quad_v1-0_B (Thai participants). The specific aims for the project are as follows: (1) To apply analytic approaches for conducting GWA mapping studies on quantitative phenotypes related to offspring size at birth (birth weight, ponderal index, head circumference and adiposity) allowing for other known influences such as gestational age, parity, and maternal weight gain. (2) To apply the above approaches to identify genetic variation that impacts maternal glucose tolerance at ~28 weeks of gestation (fasting glucose, glucose during an oral glucose tolerance test, and insulin sensitivity expressed as quantitative traits) allowing for other known influences such as maternal weight gain, parity and age. (3) To examine the interaction between maternal genes, the intrauterine environment, and fetal genes to identify interactions that modulate genetic regulation of size at birth and fetal genetic variation that impacts on maternal glucose tolerance. GWA mapping will provide initial evidence for association of specific SNPs with the quantitative traits outlined above. As low and high birth weight are not only major causes of neonatal morbidity and mortality but have also been associated with increased risk of metabolic diseases in adults, identification of genes that regulate fetal growth and maternal metabolism will provide novel information about the pathways that regulate these processes as well as important insight into susceptibility genes for chronic diseases like type 2 diabetes. The Version 1 (v1) dbGaP release will include data only from the Hispanic study participants. The Version 2 (v2) dbGaP release will include data from the Hispanic and European ancestry study participants. The Version 3 (v3) dbGaP release will include data from the Afro-Caribbean, Hispanic and European ancestry participants. The Version 4 (v4) dbGaP release will include data from all participants (i.e., Afro-Caribbean, Hispanic, European ancestry, and Thai participants). This study is part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to maternal metabolism and birthweight through large-scale genome-wide association studies of infants and their mothers at multiple international sites. Genotyping was performed at the Broad Institute of MIT and Harvard, and at CIDR of Johns Hopkins University, GENEVA genotyping centers. Data cleaning and harmonization was performed at the GEI-funded GENEVA Coordinating Center at the University of Washington.

  Study phs000096

• Rapid Whole Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units

  Monogenic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undifferentiated at birth. More than 3,500 monogenic diseases have been characterized, but clinical testing is available for only some of them and many feature clinical and genetic heterogeneity. As such, an immense unmet need exists for improved molecular diagnosis in infants. Because disease progression is extremely rapid, albeit heterogeneous, in newborns, molecular diagnoses must occur quickly to be relevant for clinical decision-making. We describe 50-hour differential diagnosis of genetic disorders by whole-genome sequencing (WGS) that features automated bioinformatic analysis and is intended to be a prototype for use in neonatal intensive care units. Retrospective 50-hour WGS identified known molecular diagnoses in two children. Prospective WGS disclosed potential molecular diagnosis of a severe GJB2-related skin disease in one neonate; BRAT1-related lethal neonatal rigidity and multifocal seizure syndrome in another infant, identified BCL9L as a novel, recessive visceral heterotaxy gene (HTX6) in a pedigree, and ruled out known candidate genes in one infants. Sequencing of parents or affected siblings expedited the identification of disease gene in prospective cases. Thus, rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling. Reprinted from Saunders et. al, Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units. Sci. Transl. Med. 4, 154ra135 (2012; PMID: 23035047) with permission from AAAS.

  Study phs000564

• The landscape of Usher syndrome-associated transcript isoforms in the human neural retina

  Usher syndrome is an autosomal recessively inherited disorder characterized by the combination of progressive loss of visual function due to retinitis pigmentosa, sensorineural hearing loss and vestibular dysfunction in a subset of cases. Usher syndrome is clinically and genetically heterogeneous. To date, eleven genes have been identified that are associated with Usher syndrome. It is known that these genes express multiple isoforms, however, for most of the known isoforms their relative importance in the human retina is unknown. To fill this gap, using PacBio long-read mRNA sequencing we aimed to provide an overview of the Usher syndrome transcripts in the human retina.

  Study EGAS50000000504

• Whole genome sequencing data of high-grade serous ovarian cancer samples (set 8a)

  Whole genome sequencing data of 26 high-grade serous carcinoma (HGSC) patients (87 samples) sequenced with MGISEQ-2000 and HiSeq X Ten.

  Dataset EGAD00001011304

• NHGRI GREGoR Consortium: Genomics Research to Elucidate the Genetics of Rare Disease

  The NHGRI GREGoR (Genomics Research to Elucidate the Genetics of Rare Disease) Consortium was established in June 2021 with the goal of developing novel tools and approaches to advance the discovery of the genetic basis of rare conditions. Numerous types of molecular data are generated in GREGoR and available on the AnVIL cloud platform via dbGaP application, including short- and long-read genome and exome sequencing, transcriptomics, metabolomics, methylomics, and proteomics. De-identified clinical and demographic data is obtained, with a focus on standardized ontologies.Visit the GREGoR Consortium data webpage for summary information about the GREGoR Dataset, including numbers of participants and data types, methods documentation, and Release Notes. The Consortium comprises five Research Centers (RCs - see below), a Data Coordinating Center (DCC), and various partner members and external collaborators.Baylor College of Medicine Research Center (BCM-GREGoR) The Baylor College of Medicine GREGoR program, which is part of the GREGoR consortium, enrolls individuals, families, and cohorts with suspected rare disease across a range of syndromic and non-syndromic phenotypes. Subjects are enrolled from national and international collaborating physician referrals. Subjects provide written informed consent for future re-contact. Data generated and shared include family structure, detailed phenotypes, exome or short-read genome data, and in some cases long-read genome or RNA-sequencing, and these are shared upon completion of standard quality control checks and annotation. Broad Institute (Broad) The Broad Center for Mendelian Genomics, part of the GREGoR consortium uses next-generation sequencing (exome, genome, transcriptome, and long read sequencing), computational approaches, and functional studies to discover the variants and genes that underlie Mendelian conditions with a particularly focus on neuromuscular, neurodevelopmental, and syndromic phenotypes. Samples come from collaborators and direct enrollment through the Rare Genomes Project and we are committed to rapid data sharing without an embargo period. University of California, Irvine (UCI-GREGoR) To accelerate the pace of Mendelian disease gene discovery and clinical implementation, we propose a Mendelian Genomics Research Center, part of the GREGoR Consortium, leveraging the broad pediatric and adult clinical and research expertise at Children's National Hospital and University of California, Irvine. Our goal is to develop best practices to increase the diagnostic yield of rare diseases, engage the community to reduce health disparities for complex diagnoses, while creating a dataset accessible to all. Our Center will unite world class experts combining basic and translational research with innovative approaches to phenotyping, variant identification and functional investigation of both coding and non-coding sequence changes with the goals of discovering novel Mendelian gene variations and identifying variants not detected on current sequencing pipelines, disambiguating uncertain variants into disease-causing versus benign categorizations, and sharing information by working collaboratively with the GREGoR community.GREGoR Stanford Site (GSS) The goal of the GREGoR Stanford Site (GSS) is to provide a platform for functional genomics research and validation to improve diagnosis in Mendelian disease. Participants included individuals with undiagnosed suspected Mendelian disease who had non-diagnostic exome sequencing and their immediate family members. Participants and their family members provided written, informed consent and biological samples from which DNA, RNA, plasma, fibroblasts, PBMCs and other cell types were generated and stored. Samples from research participants and their immediate family members may have undergone short and long-read genome sequencing, transcriptome sequencing, metabolomics and/or lipidomics profiling, methyl-capture-sequencing and ATAC-sequencing. De-identified clinical data extracted from participant medical records are linked to the samples. University of Washington Center for Rare Disease Research (UW-CRDR) The goals of the University of Washington Center for Rare Disease Research are to: (1) maximize novel gene discovery for Mendelian conditions by recruitment, short- and long-read whole genome sequencing, transcriptome sequencing and analysis of families with rare conditions for which the gene is either unknown or the gene is known but no pathogenic variant can be identified via clinical testing; (2) develop new strategies for gene discovery for Mendelian conditions caused by variants that are difficult to detect using conventional testing strategies, variants of unknown function effect (e.g., regulatory, structural variants) or have unusual modes of inheritance; and (3) implement high-throughput screening and targeted follow-up functional studies to prioritize and validate candidate non-coding variants. De-identified data and phenotypic information are shared via MyGene2, ClinVar, and AnVIL.

  Study phs003047

• ICGC PedBrain: Deep-sequencing of childhood brain tumors.

  Brain tumors constitute the childhood tumors with the highest mortality rates and survival is often associated with severe long-term sequelae due to intensive multimodal treatment regimens. Thus, the PedBrainTumor network aims at the identification of robust biomarkers for clinical management and novel molecular targets for therapeutic interventions. Using massively parallel whole-genome sequencing, and transcriptome and methylome sequencing for subsets of cases, we aim to decipher the molecular causes of medulloblastoma as well as low-grade astrocytoma, and to identify markers to stratify patients for specialized treatment. As the PedBrain network is affiliated with clinical trials in medulloblastoma and pilocytic astrocytoma, validation cohorts for the translation of key findings into clinical settings are readily available.

  Study EGAS00001000215

• NCI's Datasets for General Research Use

  This collection contains all of NCIs authorized individual-level genomic datasets currently in dbGaP that are approved for General Research Use (GRU) and have no further limitations beyond those outlined in the model Data Use Certification Agreement. Access to this study will include any additional authorized individual-level GRU datasets that become available. Renewal of this study is required annually.

  Study phs003014

• Gene expression profiles of single disseminated breast cancer cells

  A set of 56 EpCAM-positive cells derived from bone marrow aspirates of breast cancer patients or patients without a cancererous disease (30 cells from 21 M0-stage and 11 cells from five M1-stage breast cancer patients, 15 cells from seven non-cancer patients serving as controls). EpCAM-positive cells from breast cancer patients were considered disseminated tumor cells as they harbored copy number alterations and showed high expression of the epithelial marker EpCAM and the mammary luminal progenitor marker KIT in comparison to EpCAM-positive bone marrow cells from non-cancer patients. Paired-end RNA-Sequencing of the samples was performed on Illumina NovaSeq6000, raw data are provided in the Fastq format.

  Dataset EGAD00001006359

• Reference Standards for Mosaic Variant Detection

  After conception, postzygotic mutations continuously occur throughout life in humans, causing somatic mosaicism in an individual. The variant type, time of origination, and locations of the mosaic mutations result in unique mosaic patterns in a combinatorial manner and further affect phenotypes, including various noncancerous diseases. Several efforts have, thus, been made to identify the mutational landscape and mechanisms underlying the mosaic mutations. From a technical aspect, the accurate detection of mutations is at the core of the mosaicism research, and the construction of a standard reference is a critical first step to serve as the basis for analytical validation and benchmarks for germline and somatic mutation detection. Furthermore, a reference standard for mosaic mutations is urgently needed to enable more advanced research.Herein, we generated robust, large-scale, and cell line mixture-based reference standards that contain abundant mosaic SNVs and INDELs along with wild-type sites and germ line variants. Moreover, the whole reference standard set mimics the cumulative aspect of mosaic variant acquisition in the early developmental stage through a progressive cell line mixing with confirmed genotypes. It can be used for optimizing the current use of mosaic variant detection strategies, as well as developing algorithms for future improvements.We previously generated an NCBI BioProject (PRJNA758606) to release much of these data. Only the data that are subject to authorized access constraints have been included in this submission to dbGaP. The two data sources are thus, complementary to each other.

  Study phs003399

• Vaccine-Expanded Plasmablast-like B Cells Are Associated with Response to Dendritic Cell Therapy in Metastatic Melanoma

  Dendritic cells (DCs), either monocyte-derived (moDCs) or naturally circulating, have been employed in cancer treatment across both metastatic and adjuvant settings. DC vaccines (DC Vax) are capable of inducing tumor-specific immune responses, yet clinical outcomes have thus far fallen short of expectations. Here, we performed a multi-omics analysis of the apheresis product, including CD14⁺ monocytes, and the final DCVax formulation. Among all the components analyzed, the most striking finding was the unexpected presence of CD19⁺ B cells within the DC Vax formulation, which distinguished Responders from Non-Responders to moDC vaccination in metastatic melanoma. The abundance of B cells in DC Vax correlated with their peripheral frequency; however, within the vaccine, these cells acquired a CD20lowCD27hiCD38hi plasmablast-like phenotype, distinct from their autologous circulating B-cell precursors. Notably, a parallel observation was made in Responders, whose pre-treatment lesions were enriched in B cells organized as Tertiary Lymphoid Structures. These results underscore the importance of B cells in both baseline immunity and DCVax formulation, hinting at unexplored mechanisms by which they may influence vaccine effectiveness.

  Study EGAS50000001177

• NOTCH1 fusion genes in pediatric T-cell lymphoblastic lymphoma hallmark a common high-risk subgroup with blood TARC levels as possible biomarker

  T-cell lymphoblastic lymphoma (T-LBL) is a common pediatric malignancy accounting for approximately 20% of the non-Hodgkin lymphomas during childhood. Survival rates of T-LBL are ~80%, but outcome after relapse is dismal, with salvage rates reaching only ~15. Considering the extremely poor prognosis after relapse and absence of clinically relevant high-risk genetics, there is an urgent need for the identification of molecular risk factors and new prognostic biomarkers in T-LBL, as well as identification of new therapeutic strategies. In this study we present a novel entity of high-risk pediatric T-LBL patients characterized by previously unknown NOTCH1 gene fusions and highly elevated blood TARC levels

  Study EGAS00001007703

• Transcriptional_profiling_of_tauopathies_in_human_IPS_derived_neurons

  This project is a pilot study, in collaboration with Maria Grazia Spillantini and Mariangela Iovino (Cambridge Centre for Brain Repair), to investigate the utility of IPS-derived neurons for the study of neurodegenerative disorders. Our aim is to characterise the transcriptional consequences of tauopathies using neurons derived from differentiated IPSCs as a model system. We will use IPS cells derived from six individuals, four with known mutations in the tau protein, 2 without. RNA will be extracted at Day 0 and Day 65 of differentiation by which time the neuronal tauopathy is apparent. RNA will be extracted and the transcriptome of each line characterised using RNAseq. We will then search for genes that are differentially expressed between the transcriptomes of individuals with tau mutations versus those in controls. My lab will analyse the RNAseq data, comparing both affected and controls and both time-points, to establish candidate genes. Darren Logan’s lab, along with our collaborators, will experimentally verify and further investigate these genes in additional lines and animal models. From this analysis we will generate a list of candidate genes that are differentially expressed between cases and controls. This study will not only help us understand the molecular basis of tauopathies, but also identify gene candidates for biomarkers of neurodegenerative disease. It will serve as a proof of principle for future planned studies into generating and transcriptomically analysing an allelic series of Tau mutations in IPSCs with a controlled genetic background.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001000382

• Projects

  Projects Jointly managed by the European Bioinformatics Institute (EMBL-EBI) in Cambridge (UK) and the Centre for Genomic Regulation (CRG) in Barcelona, the EGA provides an invaluable service to the worldwide biomedical research community. The teams leading the EGA are involved in several international partnerships and consortia in numerous scientific fields, where they contribute to ambitious projects. In addition to the project listed below, the EGA is in a long-standing partnership with the Global Alliance for Genomics and Health (GA4GH), as described on the dedicated page. On-going projects Project Duration Domain Funder Tags CANDLE | CANDLE project aims to conceptualise and advance the development of National Cancer Data Nodes (NCDNs) in European countries. These NCDNs will boost the reuse of cancer data for research, innovation and policy making, in order to improve diagnostics and treatment for cancer patients, as well as prevention and early detection. 2025-2028 Cancer Horizon Europe DOCUMENTATION EASIGEN-DS | The EASIGEN-DS project aims to conduct a design study to establish a new European Research Infrastructure on Advanced Genomics Technologies, EASIGEN. To develop an excellent scientific, technological and operational design, we will conduct landscape studies, stakeholder consultations, and community surveying. 2025-2028 Genomic and health data Horizon Europe DATA MANAGEMENT DOCUMENTATION INFRASTRUCTURE Go-IMPaCT | Go-IMPaCT will contribute sequenced genomes and provide infrastructure as part of IMPaCT-Cohort, one of the three fundamental pillars of the Precision Medicine Infrastructure associated with Science and Technology (IMPaCT) program in Spain. Along with the Genome of Europe (GoE) project, around 18.000 people will have their genomes sequenced, also contributing to Spain's commitments in 1+MG. Go-IMPaCT will fund the development of an EGA node to manage and share this genomic and phenoclinic data, laying the foundations for regional and ethnic genomic variability in Spain to be available for research purposes. The IMPaCT cohort is created with the spirit of being an open research tool, compatible with the rest of the health research ecosystem, and other international initiatives. 2025-2027 Large-scale genomics and health data; personalised medicine Instituto de Salud Carlos III ACCESS DISCOVERY INFRASTRUCTURE METADATA STANDARDS FAIR-FEGA | This project seeks to accelerate data depositions into FEGA, significantly increasing the data flow in and from FEGA nodes. It will build capacity within the FEGA nodes and increase awareness in a wide range of stakeholders, thus altogether achieving the ultimate goal of enhancing data reuse. The project will be carried out by a strategic consortium comprising seven ELIXIR nodes and two ELIXIR communities. 2025-2026 Not applicable ELIXIR ACCESS DISCOVERY DOCUMENTATION INFRASTRUCTURE METADATA STANDARDS FEGA-Connect | A consortium of six ELIXIR nodes plus the Polish FEGA node (in-kind contribution) joining forces to build a solid base to develop solutions for effective multi-omic sensitive data integration between FEGA nodes and other infrastructures and specialised Data repositories. We aim to promote a more coherent data deposition, discoverability and retrieval of multi-omics datasets, providing FAIRer data and consequently accelerating research. 2025-2026 Multi-omics data ELIXIR ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE METADATA STANDARDS IMPaCT-Data 2 | IMPaCT-Data 2 will develop a digital platform for the integration and modelling of biomedical data associated with IMPaCT (Precision Medicine Infrastructure associated with Science and Technology) projects in Spain. It will deploy a sustainable infrastructure that facilitates the integration, standardisation, interoperability and analysis of clinical, genomic, molecular and medical imaging data. This platform will be aligned with European projects such as Genome of Europe (GoE), the first project to make use of the European Genomic Data Infrastructure (GDI), and EUCAIM. IMPaCT-Data 2 will benefit from advanced Artificial Intelligence and High Computing Capacity Systems capabilities, offering robust and accessible tools for researchers from the National Health System in Spain. 2025-2026 Large-scale genomics and health data; personalised medicine Instituto de Salud Carlos III ACCESS DISCOVERY INFRASTRUCTURE METADATA STANDARDS SenSec | This project aims to establish a mechanism for orchestrating secure access to sensitive data hosted by the EGA, whether in Central EGA or any Federated Node, from Galaxy, a popular open-source, community-driven VRE (Virtual Research Environment) for bioinformatics analysis. Building on a previous prototype that enabled Galaxy users within Trusted Research Environments (TREs) to decrypt sensitive data for workflow execution without sharing private encryption keys, SenSec will expand this prototype into a comprehensive solution for secure data analysis in Galaxy, facilitating encrypted data access and transfer from FEGA/EGA repositories to designated TREs. 2025-2026 Genomic and health data; trusted research environment ELIXIR ACCESS DATA ANALYSIS ERDERA | The European Rare Disease Research Alliance (ERDERA) takes over EJPRD to deliver concrete health benefits to rare disease patients in the next decade by advancing prevention, diagnosis and treatment research. To leave no one behind, over 170 organisations championed by the European Union and member states are working hand in hand to make Europe a world leader in rare diseases research and innovation. 2024-2034 Rare diseases Horizon Europe; "La Caixa" Foundation cofunds CRG's contribution ACCESS DATA ANALYSIS DISCOVERY INFRASTRUCTURE SYNTHIA | The aim of SYNTHIA is to deliver validated, reliable tools and methods for synthetic data generation (SDG). The tools will cover multiple data types including lab results, clinical notes, genomics, imaging and m-health data. SYNTHIA also hopes to make possible the generation of longitudinal data. 2024-2029 Genomic and health data; multi-omics; AI solutions Innovative Health Initiative (IHI) DATA ANALYSIS DATA MANAGEMENT INFRASTRUCTURE GoE | The Genome of Europe initiative aims to build a European network of national genomic reference cohorts of at least 500.000 citizens. These reference cohorts will be selected to be representative of the European population. 2024-2028 Large-scale genomic and health data Horizon Europe ACCESS DISCOVERY INFRASTRUCTURE METADATA STANDARDS HEREDITARY | HEREDITARY aims to transform the way we approach disease detection, prepare treatment response, and explore medical knowledge by building a robust, interoperable, trustworthy, and secure framework that integrates multimodal health data (including genetic data) while ensuring compliance with cross-national privacy-preserving policies. 2024-2027 Neurodegenerative disorders, gut-brain interplay Horizon Europe DATA MANAGEMENT DATA ANALYSIS EOSC-ENTRUST | The mission of EOSC-ENTRUST is to create a European network of trusted research environments for sensitive data and to drive European interoperability by joint development of a common blueprint for federated data access and analysis. 2024-2026 Trusted Research Environment Horizon Europe INFRASTRUCTURE EBV-MS | "Targeting Epstein-Barr Virus Infection for Treatment and Prevention of Multiple Sclerosis". The ambitious goals of the project are to answer the questions why only a few EBV infected persons develop MS, and define the underlying mechanism of this process, as well as clarify if targeting the EBV infection can prevent MS or improve the disease course. 2023-2028 Viral-host genetics; immune response; disease modelling; disease prevention; AI/ML solutions Horizon Europe DATA MANAGEMENT DATA ANALYSIS WISDOM | WELL-BEING IMPROVEMENT THROUGH THE INTEGRATION OF HEALTHCARE AND RESEARCH DATA AND MODELS WITHOUT BORDER FOR CHRONIC IMMUNE-MEDIATED DISEASES aims to deploy novel approaches for data processing, harmonisation, management, and secure data sharing and federated access for diseases like multiple sclerosis. Using an end-user guided approach, it will facilitate responsible and critical assessment of the use of AI in healthcare. 2023-2028 Chronic immune-mediated diseases Horizon Europe DATA MANAGEMENT INFRASTRUCTURE EUCAIM | EUropean Federation for CAncer IMages is a project that will build a highly secure, federated and large-scale European cancer imaging platform, with capabilities that will greatly enhance the potential of Artificial Intelligence in oncology. 2023-2027 Cancer Digital Europe Programme (DIGITAL) DISCOVERY CONTAGIO | CONTAGIO (COhorts Network To be Activated Globally In Outbreaks) aims to create coordination mechanisms to rapidly react to infectious disease (re-)emergence in low- and middle-income countries (LMICs). 2023-2026 Infectious Diseases European Commission - Horizon Europe ACCESS DATA MANAGEMENT DISCOVERY Youth-GEMs | Youth-GEMS (Gene Environment Interactions in Mental Health TrajectorieS of Youth) will conduct research into the genetic and environmental factors of mental health in young European people. 2022-2027 Mental health European Commission - Horizon Europe DATA MANAGEMENT DISCOVERY GDI | The European Genomics Data Infrastructure project is enabling access to genomic and related phenotypic and clinical data across Europe. It is doing this by establishing a federated, sustainable and secure infrastructure to access the data. 2022-2026 Genomic and health data European Commission - Horizon Europe; "La Caixa" Foundation cofunds CRG's contribution DISCOVERY DOCUMENTATION INFRASTRUCTURE IMPaCT-T2D | The IMPaCT-T2D project aims at studying the complete genomes of a large cohort of patients with Type 2 Diabetes mellitus (T2D), using modern sequencing technologies and artificial intelligence (AI) in order to improve the stratification and pharmacological treatment in the context of precision medicine. 2022-2025 Cardiovascular and Complex Diseases Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE Completed projects Project Duration Domain Funder Tags EOSC4Cancer | EOSC4Cancer builds on existing projects, research outcomes and established community solutions to create the federated FAIR data, analysis and services infrastructure needed for European Cancer research programmes. 2022-2025 Cancer European Commission - Horizon Europe DISCOVERY EuCanImage | A European Cancer Image Platform Linked to Biological and Health Data for Next-Generation Artificial Intelligence and Precision Medicine in Oncology. 2020-2025 AI Solutions in Oncology European Commission - H2020 Programme; "La Caixa" Foundation cofunds CRG's contribution DATA MANAGEMENT METADATA STANDARDS GenoMed4ALL | A consortium built to empower personalised medicine in the field of haematological diseases through the use of AI and the pooling of genomic and clinical data. 2020-2025 Hematological diseases European Commission - H2020 Programme DISCOVERY METADATA STANDARDS BY-COVID | The BeYond-COVID project aims to make COVID-19 data accessible to scientists in laboratories but also to anyone who can use it, such as medical staff in hospitals or government officials. Going beyond SARS-CoV-2 data, the project will provide a framework for making data from other infectious diseases open and accessible to everyone. 2021-2024 Infectious diseases European Commission - H2020 Programme ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE IMPaCT-Data | IMPaCT-Data aims to create the infrastructure for secondary use of data from Spanish healthcare systems - electronic health records, medical imaging and genomic repositories - and contribute with the knowledge and methodology produced to the healthcare system. 2021-2024 Large-scale genomics and health dataSpanish Ministry of Science and Innovation; Instituto de Salud Carlos III ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE LaMarato | It is a project aimed at creating and developing a catalan interhospitalary network to interrogate genetic variants from thousands of genetic tests carried out in patients with rare diseases from the main catalan hospitals. 2021-2024 Genomic and health data Fundacio La Marato de TV3 (catalan foundation) DISCOVERY HealthyCloud | This consortium will contribute a Strategic Agenda towards the European Health Research and Innovation Cloud. The project will work in collaboration with a broad range of stakeholders to ensure that all voices are included and that the results are technically and ethically sound. 2021-2023 Not Applicable European Commission - H2020 Programme DOCUMENTATION B1MG | Beyond 1 Million Genomes aims to create a network of genetic and clinical data across Europe. The project provides coordination and support to the 1+ Million Genomes Initiative (1+MG). This initiative is a commitment of 24 EU countries, the UK and Norway to give cross-border access to one million sequenced genomes by 2022. 2020-2023 Not applicable European Commission - Horizon Europe DATA MANAGEMENT INFRASTRUCTURE METADATA STANDARDS ELIXIR-CONVERGE | An alliance with the goal of Connecting and aligning ELIXIR Nodes to deliver sustainable FAIR life-science data management services. 2020-2023 Data Management and Infectious Diseases European Commission - H2020 Programme DATA MANAGEMENT INFRASTRUCTURE METADATA STANDARDS IHCC | The International HundredK+ Cohorts Consortium aims to create a global platform for translational research ? informing the biological and genetic basis for disease and improving clinical care and population health. 2020-2022 Translational research NIH; The Wellcome Trust; CZI INFRASTRUCTURE METADATA STANDARDS PPCG | The Pan Prostate Cancer Group aims to harmonise and interrogate Whole Genome DNA Sequence data generated around the world from over 2000 men with prostate cancer, with associated transcriptome and methylome data to include men from different clinical categories, and ethnicities. This project is about providing breakthrough advances through analysis of a very large series of Whole Genome DNA data from prostate cancer contributed by many of the leading scientists and clinicians working in prostate cancer genomics. 2019-2024 Cancer Cancer Research UK DATA MANAGEMENT CINECA | Consortium providing a Federated solution enabling population-scale genomic and biomolecular data accessible across international borders accelerating research and improving the health of individuals resident across continents. 2019-2023 Large-scale Genomics and Health Data European Commission - H2020 Programme ACCESS DATA MANAGEMENT DISCOVERY INFRASTRUCTURE EASI-Genomics | A project designed to provide easy access to cutting-edge DNA sequencing technologies to researchers from academia and industry, within a framework that ensures compliance with ethical and legal requirements, as well as FAIR and secure data management. 2019-2023 Next Generation Sequencing European Commission - H2020 Programme ACCESS EJP-RD | An European consortium built to create a comprehensive, sustainable ecosystem allowing a virtuous circle between research, care, and medical innovation. 2019-2023 Rare diseases European Commission - H2020 Programme ACCESS DATA MANAGEMENT DOCUMENTATION METADATA STANDARDS EOSC-Life | EOSC-Life brings together the 13 Life Science research infrastructures (LS RIs) to create an open, digital and collaborative space for biological and medical research. The project will publish 'FAIR' data and a catalogue of services provided by participating RIs for the management, storage and reuse of data in the European Open Science Cloud (EOSC). 2019-2023 Not applicable European Commission - H2020 Programme DOCUMENTATION EUCANCan | A federated network aiming at implementing a cultural, technological and legal integrated framework across Europe and Canada, to enable and facilitate the efficient sharing of cancer genomic data. 2019-2023 Cancer European Commission - H2020 Programme DATA MANAGEMENT METADATA STANDARDS The Federated EGA framework: supporting sensitive data management across the ELIXIR Nodes | This project is a direct continuation of the FHD IS with the goal to position the FEGA framework as the core infrastructure driver to support human data sharing for research. 2019-2023 Human genomic data ELIXIR INFRASTRUCTURE UK Biobank | UK Biobank is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. This project is to archive whole genome sequencing and other genetic data for UK Biobank participants. 2019-2023 Large-scale Genomics and Health Data The Wellcome Trust; UKRI; Amgen; AstraZeneca; GSK; Johnson & Johnson DATA MANAGEMENT INFRASTRUCTURE VEIS | The core mission of VEIS is to create an open ecosystem of technologies that will address and adapt to the requirements of the systems used to analyse and interpret -omics and clinical data in research and application environments in biomedicine. The aim of the project is to leverage the value of the EGA for both industry and society. 2019-2022 Oncology and Rare diseases Generalitat de Catalunya and European Regional Development Fund (ERDF) ACCESS DISCOVERY ELIXIR BEACON IS | This study follows on from a number of earlier activities that have established the ELIXIR Beacon Project. The main aim is to extend the Beacon protocol, developed at EGA, to become the reference ELIXIR Data Discovery product 2019-2021 Not applicable ELIXIR DISCOVERY ELIXIR FHD IS | This project coordinates the delivery of FAIR compliant metadata standards, interfaces, and reference implementation to support the federated ELIXIR network of human data resources. 2019-2021 Human genomic data ELIXIR INFRASTRUCTURE ELIXIR Rare Disease | The Rare Disease Community extends and generalises the system of access authorisation and high volume secure data transfer developed within the EGA. The goal of the Community is to create a federated infrastructure that will enable researchers to discover, access and analyse different rare disease repositories across Europe. It is doing this in partnership with other European infrastructure projects, namely RD-CONNECT, BBMRI-ERIC and E-Rare.2019-2021 Rare diseases ELIXIR INFRASTRUCTURE Solve-RD | Solve-RD - solving the unsolved rare diseases - is a research project funded by the European Commission. It echoes the ambitious goals set out by the International Rare Diseases Research Consortium (IRDiRC) to deliver diagnostic tests for most rare diseases by 2020. The current diagnostic and subsequent therapeutic management of rare diseases is still highly unsatisfactory for a large proportion of rare disease patients - the unsolved RD cases. For these unsolved rare diseases, we are unable to explain the etiology responsible for the disease phenotype, predict the individual disease risk and/or rate of disease progression, and/or quantitate the risk of relatives to develop the same disorder. 2018-2024 Rare diseases European Commission - H2020 Programme ACCESS DATA MANAGEMENT METADATA STANDARDS EuCanShare | An EU-Canada joint infrastructure for next-generation multi-Study Heart research. 2018-2022 Cardiovascular Diseases European Commission - H2020 Programme ACCESS METADATA STANDARDS

  Documentation about/projects-and-funders/projects

• NHLBI TOPMed: SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS)

  Subpopulations and Intermediate Outcome Measures in COPD Study Description Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) supports the prospective collection and analysis of phenotypic, biomarker, genetic, genomic, and clinical data from subjects with COPD for the purpose of identifying subpopulations and intermediate outcome measures. It is funded by the National Heart, Lung, and Blood Institute and is coordinated by the University of North Carolina at Chapel Hill. Molecular fingerprinting and extensive subject phenotyping will be performed to identify disease subpopulations and to identify and validate surrogate markers of disease severity, which will be useful as intermediate outcome measures for future clinical trials. Secondary aims are to clarify the natural history of COPD, to develop bioinformatic resources that will enable the utilization and sharing of data in studies of COPD and related diseases, and to create a collection of clinical, biomarker, radiographic, and genetic data that can be used by external investigators for other studies of COPD. Participating Institutions: Research participants for SPIROMICS will be enrolled, phenotyped, and followed at twelve SPIROMICS Clinical Centers: Columbia University, Temple University, Johns Hopkins University, Wake Forest University, University of Michigan, University of Illinois at Chicago, University of Iowa, University of Utah, National Jewish Health, University of California at San Francisco, and University of California at Los Angeles. The University of North Carolina at Chapel Hill serves as the Genomics and Informatics Center. The Radiology Reading Center is based at the University of Iowa. The PFT Reading Center is based at the University of California at Los Angeles. Study Design: SPIROMICS is a prospective cohort study that enrolled approximately 2,981 participants at twelve clinical centers over five years. Participants are distributed across four enrollment strata (i.e., Never-smokers, Smokers without COPD, Mild/Moderate COPD, and Severe COPD). Study Visits: Participants have up to four in-person visits (Baseline and Annual Clinic Visits at years 1, 2, 3 after Baseline). Study questionnaires and spirometry are completed at all main study visits. Blood and urine samples are collected at visits 1, 2, and 4. Sputum samples are collected at Visit 1. The CT scans are completed and Baseline and Visit 2. Participants also receive quarterly follow-up calls to assess health status and determine if an exacerbation has occurred. Substudies Bronchoscopy and Immunophenotyping Substudy The Bronchoscopy Substudy will enroll 50 subjects per site, for a total of 300 participants. These participants will be recruited across all four study strata. This substudy includes two study visits. During the first visit, sputum samples are collected for Immunophenotyping analysis at the Immunophenotyping Core Lab based at the University of Michigan. Participants then return for a second visit during which samples are collected via bronchoscopy, including bronchoalveolar lavage, epithelial brushings and bronchial biopsies. Immunophenotyping analysis is also conducted on BAL and blood collected during the bronchoscopy study visit. Repeatability Substudy The entire baseline clinic visit was repeated on 98 volunteers to determine reliability of measurement procedures. All baseline study-related procedures and questionnaires, including the CT scan, were re-administered and new samples of blood, urine, saliva, and sputum were collected. Field center staff processed these biospecimen samples according to the same protocol. Exacerbation Substudy The Exacerbation Substudy is a prospective, longitudinal observational study of up to 400 participants, which will allow the assessment of participant-driven health care utilization (HCU) events and symptom-defined exacerbation events over time. HCU-driven events are defined by change in medical treatment in response to a perceived COPD Exacerbation. Symptom-based events will be defined by using EXACT-PRO (EXacerbations of Chronic Pulmonary Disease Tool - Patient Reported Outcome), a daily symptom diary developed to measure the frequency, severity, and duration of exacerbations in clinical trials. All participants are provided with a PDA on which to complete the diary. Participants reporting a possible COPD exacerbation will be brought into the study clinic for a study visit to collect biological specimens and questionnaire data. The overall objectives of the Exacerbation Substudy are to: Obtain clinical data and specimens on SPIROMICS participants before and during an acute COPD exacerbation defined by Health care utilization triggered by the subject, or Symptomatic change (triggered by an EXACT defined threshold) Describe symptomatic changes occurring around HCU and symptom-defined (EXACT) events and their relationship to clinical and specimen data, Characterize the non-exacerbation "stable" state in COPD using the EXACT, including: Symptom variability (EXACT), Clinical data and specimen parameters during a stable state (baseline), The relationship between clinical and specimen data and symptom severity and variability. Explore the characteristics of stable patients, defined as those who do not experience HCU or symptom-defined (EXACT) events during the sub-study period, using baseline clinical data and specimens, and compare these characteristics with patients who experience HCU and/or symptom-defined events. Examine the relationship between HCU and symptom-defined exacerbation frequency during the first one-year period of follow-up for exacerbations and health outcomes, including 12-month change in lung function and COPD health status, and longer-term morbidity and mortality, with the latter derived from long-term data from the larger SPIROMICS study.

  Study phs001927

• Consanguinity and rare mutations outside of MCCC genes underlie non-specific phenotypes of MCC Deficiency

  3-Methylcrotonyl-CoA Carboxylase Deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism, which has a highly variable clinical phenotype, ranging from acute metabolic acidosis to non-specific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD. We performed exome sequencing on DNA from 107 healthy controls and 33 cases. We examined these data for associations between either MCC mutational status, genetic ancestry or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases. We determined that individuals with non-specific clinical phenotypes are highly inbred compared to cases that are asymptomatic and healthy controls. For five of these individuals we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their non-specific clinical phenotypes previously attributed to MCCD.

  Study phs000776

• Metagenomic Analysis of the Structure and Function of the Human Gut Microbiota in Crohn's Disease

  Inflammatory bowel diseases (IBD), such as Crohn's disease, are chronic, immunologically mediated disorders that have severe medical consequences. The current hypothesis is that these diseases are due to an overly aggressive immune response to a subset of commensal enteric bacteria. Studies to date on IBD have suggested that the disorder may be caused by a combination of bacteria and host susceptibility; however the etiologies of these diseases remain an enigma. In this application, we propose to develop and demonstrate the ability to profile Crohn's disease at an unprecedented molecular level by elucidation of specific biomarkers (bacterial strains, genes, or proteins) that correlate to disease symptoms. To achieve this goal, we will employ a multidisciplinary approach based on metagenomic and metaproteomic molecular tools to elucidate the composition of the commensal microbiota in monozygotic twins that are either healthy or exhibit Crohn's disease (for concordant, both are diseased; for discordant, one is healthy and one is diseased). The central hypotheses of this proposal are (1) that specific members and/or functional activities of the gastrointestinal (GI) microbiota differ in patients with Crohn's disease as compared to healthy individuals, and (2) that it will be possible to elucidate microbial signatures which correlate with the occurrence and progression of this disease by integration of data obtained from 16S rRNA-based molecular fingerprinting, metagenomics, and metaproteomics approaches. To address these hypotheses, three specific aims are proposed: 1) Obtain data on community gene content (metagenome) in a subset of healthy twins and twins with Crohn's Disease to assess potential differences in the metabolic capabilities of the gut microbiota associated with CD, 2) Obtain data on community protein content (metaproteome) in a subset of healthy twins and twins with Crohn's Disease to assess the state of expressed proteins associated with CD, 3) Apply various statistical clustering and classification methods to correlate/associate microbial community composition, gene and protein content with patient metadata, including metabolite profiles and clinical phenotype. The ultimate goal of these efforts is to identify novel biomarkers for non-invasive diagnostics of CD and to eventually identify drug targets (i.e. bacterial strains) for cure or suppression of disease symptoms. PUBLIC HEALTH RELEVANCE: This study aims to unravel the contribution of the bacteria that normally inhabit the human gastrointestinal tract to Crohn's disease by using a multidisciplinary approach to study changes in the structure and function of gut microbial communities in three sets of patient cohorts who have Crohn's disease. These results will be compared with those obtained from the study of healthy individuals and have the potential to identify new biomarkers of disease severity, location, and progression.

  Study phs000257

• Genome-Wide Assessment of DNA Methylation in Systemic Lupus Erythematosus-Related Autoantibodies

  Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can have debilitating effects on multiple organ systems. In SLE, the pivotal immunologic disturbance is the formation of autoantibodies directed against nuclear and cellular antigens. These autoantibodies are associated with specific organ manifestations. Our previous work has shown that certain single nucleotide polymorphisms (SNPs) are associated with the production of SLE-related autoantibodies. However, these genetic associations do not completely explain autoantibody development in SLE. Therefore, we examined whether epigenetic factors such as DNA methylation may be associated with the development of SLE-related autoantibodies. In this study, we examined whether differential DNA methylation is associated with anti-dsDNA, anti-SSA/Ro, anti-Smith, and anti-RNP autoantibodies. Using the Illumina HumanMethylation450 Beadchip, over 450,000 DNA methylation sites were characterized in 325 female SLE cases of European descent. Using a multivariable regression analyses, the methylation status of 16 CpG sites in 11 genes was found to be associated with the SLE-related autoantibodies under study. This study shows that epigenetic factors are associated with autoimmune disease phenotypes, and epigenetic studies are a complementary method to genetic association studies for understanding the biologic mechanisms contributing to autoimmune disease.

  Study phs000947

• Genotypic data of the individuals in HPP project

  Dataset contains imputed SNP genetics data for human phenotype project https://humanphenotypeproject.org/. The samples are genotypes of 8958 individuals that underwent genetic sequencing based on buccal swab.Sequencing is performed at Neogen GeneSeek Laboratories using Illumina Novaseq at low-pass, targeting coverage levels of 0.5× and 1×. Imputation was done using loimpute-v0.1.0 over the aligned reads. Imputation is done for the autosomal chromosomes (1-22) using The 1000 Genomes phase 3 haplotypes (1KGP3) as a reference panel. The samples are provided in merged PLINK 1 binaries (.bed/.bim/.fam)

  Dataset EGAD00010002714

• Whole exome sequencing of bladder tumors

  Bladder carcinomas are immunogenic, and patients with bladder cancer benefit from immune checkpoint therapy. This is correlated to a high tumor mutation burden, which provides a higher number of neoepitopes that can be recognized by tumor-specific CD8+ T cells. Intravesical Bacillus Calmette-Guérin (BCG) is used to treat non-muscle invasive bladder cancer (NMIBC), but its mechanism of action remains elusive. Most lymphocytes appearing in the urine of BCG-treated patients are CD4+ T cells though preclinical studies showed that CD8+ T cells are also necessary for BCG treatment efficacy. It is currently unknown which proportion of patients with non-metastatic bladder cancer develop a spontaneous antitumor CD8+ response, and if BCG treatment influences this response. were prepared using the xGen Dual Index UMI Adapters (IDT), and genomic DNA (gDNA) extracted (DNeasy kit, Qiagen) from formalin-fixed paraffin- embedded (FFPE) or snap-frozen tumor tissue, as well as autologous lymphocytes. Libraries were subjected to paired-end sequencing using Illumina HiSeq4000 with a coverage depth of 250X. Library preparation was carried out with the AllType FASTplex NGS 11 Loci Flex Kit (One Lambda), and sequencing was conducted on the Illumina MiSeq platform.

  Study EGAS50000001248

• Assessment of Health-related Quality of Life in Rare Kidney Stones

  The purpose of this study is to learn about Health-related Quality Of Life (HRQoL) in patients enrolled in the Rare Kidney Stone Consortium (RKSC) registries. Quality of life studies look at different aspects of both physical and mental components of people's lives. HRQoL data for people affected by kidney stones are not currently available for people followed over time. All participants enrolled in the RKSC registries will be invited, via email or postal mail, to participate in this study. Health-related quality of life in people with rare kidney stones enrolled in the RKSC registries will be measured. Instruments used in this study are the SF-10 for pediatric participants and SF-36v2 for adult participants. The surveys will be completed online. Participants without a computer or internet access will participate using a paper version of the survey. These surveys will be done at enrollment and annually thereafter. The SF-36v2 includes 36 questions and is estimated to take 15 minutes for its completion, while the SF-10 includes 10 questions and could be completed in 5 minutes. The research questions are: Assessment of HRQoL in patients with rare kidney stones. Comparison of HRQoL results between rare kidney stone formers, general population and other populations with relevant chronic diseases. Comparison of HRQoL results in the same populations affected by different stones and analyzed with attention to the effects of various factors included in the disease registry, such as stone activity, burden of urologic interventions, medication and other treatments. Evaluation of HRQoL and its trends over time in patients undergoing treatment for rare kidney stones. About this study: The plan is to have 400 participants from all four registries take part in this multi-center study. The assessment of your HRQoL will be done annually for 5 years.

  Study phs001770

• A Phase I/II Study of Revlimid (lenalidomide) in Combination with Vidaza (azacitidine) in Patients with Advanced Myelodysplastic Syndrome (MDS)

  This single-arm study design has been selected to investigate the safety of combination therapy with Vidaza® (azacitidine) and Revlimid® (lenalidomide) in a population of 18 participants with advanced MDS for the Phase I portion, and 18 participants for the Phase II portion. The multi-center nature of the study should enhance the general applicability of the results. Participants with advanced MDS were chosen because it is expected that the combination of the two drugs will by myelosuppressive, which can be considered a necessary toxicity to effect improvements in PR and CR rates in this advanced population, akin to participants with AML. Finally, the combination was chosen to be studied because currently available therapies in this population, and their effectiveness, are limited, and single-agent Vidaza® (azacitidine), while effective at delaying transformation to AML or death, is not curative. The doses of Revlimid® (lenalidomide) in this study are similar to those that were demonstrated to have an effect and to be well-tolerated in participants with MDS. Doses for Vidaza® (azacitidine) are similar to those used in the pivotal trial, though for a 5-day treatment period instead of 7 to minimize toxicity for the first 3 blocks of participants, and then at a lower dose over a protracted period of time to explore the safety of a 10-day treatment course.

  Study phs001318

• Single Cell Analysis of Sporadic Human Basal Cell Carcinomas

  To explore tumor heterogeneity in sporadic human basal cell carcinoma tumors, we profiled three individual patient tumors by scRNA-Seq and scATAC-Seq. Basal cell carcinomas (BCCs) are driven by hedgehog signaling with GLI1 representing the key downstream transcription factor that drives tumor growth. GLI1 as such is a readout of active hedgehog signaling. We identified that LY6D can mark squamous populations such as in squamous cell carcinomas (SCCs) that are negative for GIL1 and hedgehog signaling. As such, both GLI1 and LY6D can be used as biomarkers of BCCs and SCCs and their related states.

  Study phs003103

• Pathogenic Neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq

  Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. an in-house developed tool (QURNAS) was used to calculate the enrichment score (ERS) for each splicing event. RNA enrichment of NF1 and SPRED1 was done using SPET (NUGEN - NF1 only) and using SureSelect (Agilent - NF1 and SPRED1).

  Study EGAS00001005530

• Airway Epithelial Cell Culture RNA Expression

  This study seeks to characterize airway epithelial mRNA and miRNA expression under a variety of experimental conditions. Samples are available from primary human cell cultures as well as cell lines grown under a variety of experimental conditions as documented in the phenotype and conditions associated with each individual sample. For some experiments, cells on plastic were exposed to cigarette smoke condensate to evaluate the effects of smoking. FOSL1 is a target gene for regulation by MIR34A family microRNAs.

  Study phs002472

• Kids First: Congenital Heart Defects and Laterality Birth Defects

  Laterality defects occur in approximately 1:10,000 newborns and are associated with a range of structural birth defects and abnormalities of organ positioning. Gut malrotation, biliary atresia, asplenia or polysplenia, complex cardiovascular malformations, and midline defects such as neural tube defects, vertebral anomalies and rib fusions are found in various combinations in patients with laterality defects. In addition, a subset of laterality defects caused by abnormalities of cilia position or function are associated with additional medical problems such as chronic sinusitis and bronchiectasis that require specific preventive care; however these patients frequently are undiagnosed until late in disease course. The goal of this project is to elucidate the genetic architecture of laterality disorders in order to inform medical management and risk stratification and to prevent complications. Laterality disorders are genetically heterogeneous and we and others have previously identified single nucleotide variants inherited in an X-linked or autosomal recessive manner as explanations for a minority of cases. In addition, we have demonstrated copy number variants (CNVs) as a mechanism of disease that requires additional investigation. We hypothesize that the majority of cases result from complex genetic inheritance. We propose to investigate this hypothesis using a multifaceted analysis approach in our extremely well phenotyped cohort of 538 probands with laterality disorders. Nested within this cohort are 105 trios who have not had previous sequencing, probands who have had exome sequencing and are excellent candidates for gene discovery via whole genome sequencing (WGS), and families with multiple affected family members for family-based analysis. All trios will be analyzed by transmission disequilibrium test (TDT) including rare variant TDT. De novo mutations will also be identified from trios for potential gene discovery. Using all probands, we will identify the prevalence of pathogenic CNVs. In addition, we will perform burden analyses to identify genes, gene interactions, and pathways important for susceptibility to laterality disorders. Finally, our rare families with multiple affected members will be studied using family based segregation analysis. This comprehensive genetic analysis in patients with laterality disorders is necessary to identify the appropriate clinical diagnostic testing for risk stratification, to elucidate underlying genetic architecture and facilitate novel gene discovery, and to provide essential knowledge about genes and pathways impacting the development of laterality disorders.

  Study phs002589

• Genotyping NIGMS CEPH Samples from the United States, Venezuela, and France

  The Human Genetic Cell Repository (HGCR) is sponsored by the National Institute of General Medical Sciences (NIGMS) with the mission of supplying scientists with the materials for accelerating disease gene discovery and functional studies. The resources available include highly-characterized, contaminant-free fibroblast cell lines, transformed lymphoblastoid cell lines (LCLs), and DNA samples derived from these cultures. While the Repository has a major emphasis on inherited diseases, it also contains large collections of cell lines gathered from populations around the world that are intended for use in facilitating the understanding of human variation. Prominent among these resources is the CEPH Reference Family collection contributed by the Centre d'Etude du Polymorphisme Humain (CEPH), Foundation Jean Dausset, Paris, France. The CEPH collection includes families collected by R. White (Utah), J. Dausset (French), J. Gusella (Venezuelan), and J. Egeland (Amish). There are a total of 809 individuals accounting for 832 pedigree positions in the reference families. Family relationships for the 61 reference families were verified at Coriell and approved by CEPH. In an effort to enhance the value of this cell culture resource available from the Repository, the Coriell Genotyping and Microarray Center used the Affymetrix Genome-Wide Human SNP Array 6.0 platform to genotype 181 samples from the NIGMS HGCR CEPH collection. Included are thirteen families from the United States (Amish Pedigree 884 and Utah Pedigrees 1331, 1356, 1400, 1416, 1424, 1427, 1477, and 1582), France (Pedigrees 35 and 66), and Venezuela (Pedigrees 102 and 104). Twelve of the families consist of 3 generations and one family consists of 2 generations. Pedigree charts and sample descriptions are available on the Repository catalog website (see below).

  Study phs000268

• Peripheral blood DNA transcriptomics of ustekinumab treatment response in patients with Crohn's disease

  Data pertains longitudinal transcriptomic data measured from blood obtained from patients with Crohn's disease that were starting treatment with ustekinumab. Samples were obtained prior to treatment and approximately 26 weeks into treatment during response assessment. At response assessment, patients were classified as responders (R) or non-responders (NR) based on a strict combination of endoscopic, biochemical and clinical criteria: ≥50% reduction in the endoscopic SES-CD score, corticosteroid-free clinical remission (≥3 point drop98 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 mg/L and fecal calprotectin ≤250 µg/g). Modified response was defined as a combination of corticosteroid-free clinical- (HBI ≤4) and biochemical (CRP ≤5 mg/L and/or fecal calprotectin ≤250 µg/g) remission between week 26-52 without treatment change through week 52. Transcriptomic analyses was conducted through RNA sequencing, wherein mRNA was extracted utilizing the QIAsymphony system, converted into cDNA and sequenced in a paired-end format on the Illumina NovaSeq6000 at the Amsterdam UMC Core Facility Genomics, generating a dataset comprising 40 million 150 bp-reads.

  Dataset EGAD50000000386

• Peripheral blood DNA transcriptomics of vedolizumab treatment response in patients with Crohn's disease

  Data pertains longitudinal transcriptomic data measured from blood obtained from patients with Crohn's disease that were starting treatment with vedolizumab. Samples were obtained prior to treatment and approximately 26 weeks into treatment during response assessment. At response assessment, patients were classified as responders (R) or non-responders (NR) based on a strict combination of endoscopic, biochemical and clinical criteria: ≥50% reduction in the endoscopic SES-CD score, corticosteroid-free clinical remission (≥3 point drop98 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 mg/L and fecal calprotectin ≤250 µg/g). Modified response was defined as a combination of corticosteroid-free clinical- (HBI ≤4) and biochemical (CRP ≤5 mg/L and/or fecal calprotectin ≤250 µg/g) remission between week 26-52 without treatment change through week 52. Transcriptomic analyses was conducted through RNA sequencing, wherein mRNA was extracted utilizing the QIAsymphony system, converted into cDNA and sequenced in a paired-end format on the Illumina NovaSeq6000 at the Amsterdam UMC Core Facility Genomics, generating a dataset comprising 40 million 150 bp-reads.

  Dataset EGAD50000000385