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• Selenium Chemoprevention: Benefits and Harms

  Selenium is a trace element that may have anti-carcinogenetic effect, but heterogenous treatment effects have been observed. This genome-wide association study investigates if genetic variation modifies the effect of selenium chemoprevention in the Selenium and Celecoxib Trial, a randomized, double-blind, placebo-controlled trial conducted at the University of Arizona Cancer Center. The objective of the clinical trial was to determine whether daily intake of 200 µg/d of selenium as a supplement could reduce the risk for developing metachronous colorectal adenomas. The study participants were recruited between 2001 and 2011. Genome-wide association study was performed for 1,323 study participants who provided blood sample at the time of study entry.

  Study phs002283

• Mega-GWAS ALS I

  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder clinically characterized by rapidly progressive paralysis and death due to respiratory failure, typically within two to three years of symptom onset. The number of ALS cases across the globe will increase to nearly 400,000 in 2040, predominantly due to aging of the population. Unraveling the genetics underlying ALS provides insights into the cellular mechanism leading to motor neuron death and provides targets for therapeutic intervention. We performed a genome-wide association study involving a meta-analysis of 20,806 ALS cases and 59,804 controls. The current study release makes available genotype data of the 15,480 subjects assayed in the Laboratory of Neurogenetics for this effort.

  Study phs000101

• Genomic Evolution of Breast Cancer Metastasis and Relapse

  Recurrent breast cancer is almost universally fatal. We characterize 170 patients locally relapsed or distant metastatic cancers using massively parallel sequencing. We identify that the relapse-seeding clone disseminates late from the primary tumor. TP53 and AKT1 appear to be enriched in ER-positive cancers predisposed to relapse. Mutation acquisition continues at relapse as the same mutation signatures continue to operate and new signatures, such as that caused by radiotherapy appear de novo. In 49% of cases we identify drivers mutations private to the relapse and these are sampled from a wider range of cancer genes, including SWI-SNF complex and JAK-STAT signaling.

  Dataset EGAD00001002698

• CD74-NRG1 fusions in lung adenocarcinoma

  We discovered a novel somatic gene fusion, CD74-NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74-NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-beta3, thereby providing the ligand for ERBB2-ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (p<0.0001). Ectopic expression of CD74-NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K-AKT pathway, and led to increased colony formation in soft agar. Thus, CD74-NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.

  Study EGAS00001000653

• Establishment and characterization of circulating tumor cells-derived organoids from metastatic breast cancer patients.

  Over the last decade, molecular stratification and associated therapies have greatly improved the treatment options and prognosis of patients diagnosed with breast cancer. However, metastatic disease remains incurable. Breast cancer cells mainly spread to the lung, liver, bone and brain and circulating tumor cells (CTCs) that migrate in the lymphatics or blood have been implicated as the cellular source of metastasis. Detailed molecular and functional characterization of patient CTCs remains poor due to their low number in patient’s bloodstream. In addition, CTCs are difficult to culture and expand ex vivo. Here we have established a novel method for culturing and unlimitedly expanding breast cancer patient-derived CTCs in CTC-derived organoids (CDOs). Our platform can serve as a foundation for serial longitudinal isolation and expansion of breast cancer cells from peripheral blood. This may enable the identification and functional validation of therapy resistance mechanisms during disease progression, which can be used for new approaches in precision medicine.

  Study EGAS00001007582

• Spatial transcriptomics of 1 untreated prostate cancer.

  Two sections of cryopreserved prostate cancer tissue from one untreated prostate cancer patient were profiled for spatial transcriptomics using the Visium Spatial library preparation protocol from 10x Genomics. The GRCh38 aligned sequencing reads from the two prostate cancer tissue sections are provided as BAM files.

  Dataset EGAD00001007921

• Exome sequencing of tumor DNA samples from patients with BPLL

  DNA extracted from sorted CD19+ tumor cells (16 patients) was used for exome capture with the SureSelect V5 All Exon Kit following the standard protocols. Paired-end sequencing (2 x 100 bp) was performed using HiSeq2000 sequencing instruments. The files are in FASTQ format.

  Dataset EGAD00001004410

• MGRB dataset

  This dataset comprises 2570 whole genome sequenced samples from the Medical Genome Reference Bank. https://sgc.garvan.org.au/initiatives/mgrb The files are provided in cram format, aligned to hs37d5 with decoys, with no further processing applied. The dataset also contains phenotype information for each sample.

  Dataset EGAD00001004940

• Exome sequencing of tumor DNA samples from patients with Waldenstrom macroglobulinemia

  DNA extracted from sorted CD19+ tumor cells (18 samples - 16 patients) was used for exome capture with the SureSelect All Exon Kit following the standard protocols. Paired-end sequencing (2 x 100 bp) was performed using HiSeq2000 sequencing instruments. The files are in FASTQ format.

  Dataset EGAD00001005322

• Spatial_transcriptome_analysis_of_Paediatric_Thymus

  Cell atlas of Paediatric Thymus Cell atlas of Paediatric Thymus - The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. We aim to interrogate the cellular composition and molecular regulators underpinning a cells identity through; genetic and genomic analysis, expression analysis, non-identifiable video imaging and cell line and organoid production, as well as, computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequently validate these findings in situ using spatial genomic and imaging technologies e.g. immunohistochemistry, RNAscope, in situ sequencing and spatial transcriptomic analyses. 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 EGAS00001004281

• Bulk RNA sequencing of 36 multi-region IPMN–PDAC tumours comprising 160 sequencing runs

  This dataset contains bulk RNA sequencing data generated from 36 multi-region tumour samples obtained from patients with intraductal papillary mucinous neoplasms (IPMN) and associated pancreatic ductal adenocarcinoma (PDAC). A total of 160 sequencing runs are included. Libraries were prepared from poly(A)-selected RNA and sequenced on an Illumina platform. The data are provided as raw sequencing files for downstream transcriptomic analyses.

  Dataset EGAD50000002215

• Genetics of Pigmentation in Eastern and Southern African Populations Study

  The goal of this study was to identify genes and loci associated with pigmentation in African populations. It comprises 1,593 participants from Ethiopia, Tanzania, and Botswana. Sexes are evenly represented (768 males and 825 females) and self reported ages ranged from 18 to 103. Mean age was used for individuals without ages. For each participant, a DSM II color meter was used to measure underarm skin reflectance in triplicate. These measures averaged and converted to a melanin index (MI = 100 x log10(1/(x/255)). All individuals were included in a genome wide scan that accounted for age, sex, and genetic relatedness.

  Study phs001396

• Spatiotemporal Transcriptome of the Human Brain

  Comprehensive knowledge about the spatiotemporal dynamics of the brain transcriptome is essential for a better understanding of neurodevelopment, sexual dimorphism, and evolution, as well as our increased susceptibility to certain brain disorders. We generated and analyzed genome-wide exon-level transcriptome data from 16 brain regions of 57 postmortem human brains, spanning from embryonic development to late adulthood and representing males and females of multiple ethnicities. We also performed genome-wide genotyping of 2.5 million SNPs and assessed genome normality for all donors. This study provides a comprehensive, publicly available dataset on the spatiotemporal human brain transcriptome and new insights into the transcriptional foundations of human neurodevelopment.

  Study phs000406

• Acute Respiratory Distress Network (ARDSNet) Studies 06 and 08 Prospective, Randomized, Multicenter Trial of Aerosolized Albuterol Versus Placebo for the Treatment of Acute Lung Injury (ALTA) (ARDSNet-ALTA-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Biospecimens Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from ARDSNet-ALTA include Plasma, DNA, Urine, and BAL. Please note that use of biospecimens in genetic research is subject to a tiered consent. Objectives This clinical trial was designed to test the hypothesis that an aerosolized beta-2-agonist, albuterol, would improve clinical outcomes in participants with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Background In participants with acute lung injury and acute respiratory distress syndrome (ALI/ARDS), inflammation of the pulmonary circulation increases vascular permeability. Fluid leaks from blood vessels into the pulmonary interstitium and alveoli. Recovery from this form of acute respiratory failure requires that the pulmonary edema resolve. The resolution of alveolar edema is driven by active transport of sodium and chloride ions from the luminal space across both type I and type II alveolar epithelial cells, creating an osmotic gradient for the reabsorption of water. In the ex vivo human lung, the rate of alveolar fluid clearance can be doubled by treatment with a cyclic AMP beta-2 adrenergic receptor agonist. On the basis of the preclinical observations that treatment with beta-2-agonists could reduce pulmonary edema and accelerate the rate of alveolar fluid clearance, the ALTA study was designed and undertaken with the hypothesis that treatment of participants with ALI/ARDS with beta-agonist therapy would accelerate the resolution of alveolar edema and improve clinical outcomes. Participants There were 282 participants. Design Study staff conducted a multicenter, randomized, placebo-controlled clinical trial in which participants were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. Conclusions Ventilator-free days were not significantly different between the albuterol and placebo groups. The results suggest that aerosolized albuterol does not improve clinical outcomes in participants with ALI. Routine use of beta-2 agonist therapy in mechanically ventilated participants with ALI cannot be recommended (Matthay, et al., 2011, PMID: 21562125).

  Study phs003743

• WES IDC samples

  PDX samples of breast cancer IDC mouse models created from patient tumor material of the NKI. Genomescan prepared the samples according to the procedure for Hybridization Capture using the Agilent SureSelectXT Human All Exon V7 kit. The prepared libraries were sequenced with Illumina sequencing technology. The samples are in fastq format and consist of the following PDX samples: IDC001, IDC125, IDC147, IDC200, IDC233, IDC244, IDC251, IDC272, IDC278, IDC281 and ILC120.

  Dataset EGAD50000001148

• Comprehensive Analysis of Structural Variants in Breast Cancer Genomes Using Single Molecule Sequencing

  This study used the SKBR3 breast cell line and tumor/normal organoids derived from breast tissue to explore the utility of long read sequencing for detecting structural variants in complex samples. Three technologies were used to characterize the samples: Illumina/10X, Pacific Biosciences, and Oxford Nanopore. Methylation results were derived from the Oxford Nanopore data. It is hoped that this resource will better help researchers better understand the utility of long read sequencing in cancer samples.

  Study phs002210

• Deep RNA sequencing in CLL

  Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical and biological behavior. We have performed deep RNA sequencing in different subpopulations of B-lymphocytes from healthy individuals and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. The transcriptomic architecture of CLL uncovered here refines the biological characterization of the disease and opens new perspectives for the clinical management of patients.

  Study EGAS00001000374

• The_British_Autozygosity_Populations_BioResource

  This data set contains whole exome sequences of individuals with self-stated parental relatedness from the East London Genes & Health cohort. Rare frequency functional variants in these healthy individuals will be studied with respect to the genetic health of the participants and loss-of-function analysis of human genes. 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 EGAS00001002742

• IBD Whole Genome Sequencing Phase 1 (2018-08-03)

  We will sequence at 15X coverage the genomes of 960 IBD patients. These samples are currently onsite at Sanger and made available for sequencing via our collaboration with the UK IBD Genetics consortium. During the next quinquennium we intend to sequence the genomes of many thousand IBD patients and these 960 represent the first stage of this effort. Ultimately we will perform association tests comparing these genomes to similar numbers of control genomes to identify rare and low-frequency variants underlying IBD. . This dataset contains all the data available for this study on 2018-08-03.

  Dataset EGAD00001004272

• Isotype-resolved sequencing of B-cell receptor in sorted memory populations (2017-09-13)

  Optimisation of ex vivo Memory B cell Expansion/Differentiation for Interrogation of Rare Peripheral Memory B Cell Subset Responses 1) 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 please see http://www.sanger.ac.uk/datasharing/ This dataset contains all the data available for this study on 2017-09-13.

  Dataset EGAD00001003747

• RNAseq of baseline tumor tissue obtained during TUR to identify biomarkers for ICB response in MIBC

  RNAseq of baseline tumor tissue obtained during TUR to identify biomarkers for ICB response in MIBC. Constitutes the entire NABUCCO phase 1B clinical trial cohort. The NABUCCO 1 trial contains 18 single-end RNA sequenced samples and 6 paired end RNA sequenced samples. The NABUCCO 2 trial contains 25 paired end RNA sequenced samples. The file type for all of the samples is FASTQ. For single end RNA sequencing, Illumina HiSeq 2500 was used as the sequencing platform. For paired end RNA sequencing, the Illumina NovaSeq 6000 was used as the sequencing platform.

  Dataset EGAD50000002556

• Tissue and Fluid Analysis in Ocular Inflammatory Disease

  Granulomas are found in multiple infectious and non-infectious human diseases, yet the pathogenic drivers of granulomatous disease are still poorly understood. To enrich for pathologic inflammatory cells, we leveraged the intrinsic immunologic isolation of the eye by examining granulomatous uveitis, a form of ocular inflammation. We performed single-cell RNA-sequencing to obtain an unbiased gene expression survey of ocular immune cells in the anterior chamber of four live human donors with granulomatous uveitis. We paired this with antigen-receptor sequence analysis to identify clonally expanded lymphocytes. Each individual had robust clonal expansion arising from a single T or B cell lineage, suggesting distinct pathogenic processes in each patient. This variability in clonal expansion was mirrored by individualized combinations of TH1, TH1/TH17, and Tregs in ocular CD4 T cells. In contrast, ocular CD8 T cells were more transcriptionally similar across donors. Finally, clonally expanded, activated B cells displayed evidence of plasmablast differentiation and class-switching within the ocular microenvironment. Collectively, our study identified conserved and individualized features of granulomatous inflammation, illuminating parallel pathophysiologic mechanisms.

  Study phs002449

• Center for Common Disease Genomics (CCDG) - Cardiovascular: BioImage Cohort

  The genetic basis of cardiovascular disease in individuals of non-European ancestry remains largely unknown. Availability of ethnically diverse study populations is essential to fully investigate the underlying causes of disease. The BioImage Study enrolled adults aged 55-80 in a prospective observational study. Subjects had no prior history of cardiovascular disease, but were identified to be at intermediate to high risk for atherosclerotic cardiovascular events (PMID: 25790876). The recruiting target was a cohort with similar demographics to the US population in terms of race and ethnicity. Produced as part of the NHGRI Centers for Common Disease Genomics, this study contains whole genome sequence data and variant calls from 922 African American participants of the BioImage Study.

  Study phs002325

• ESGI - Whole Genome Sequencing of samples from the ORCADES cohort (X10) (2019-08-19)

  Deep whole genome sequencing of sampels from the Orkney Complex Disease Study (ORCADES), each with data on up to 300 quantitative traits and other risk factors associated with cardiovascular, metabolic and other complex diseases. The samples are sequenced using the Illumina HiSeq X Ten system. . This dataset contains all the data available for this study on 2019-08-19.

  Dataset EGAD00001005269

• EGAD00010000624

  A new beta-globin mutation responsible of a beta-thalassemia (HbVar database ID 2928) was observed in 8 unrelated French families. The mutation carriers originated from Nord-Pas-de-Calais, a Northern French region where the chief town is Lille. 5 unrelated mutation carriers were genotyped for a set of 12 microsatellites from chromosome 11, around the beta-globin gene. Among the 5 mutation carriers, 4 were genotyped for 97 European Ancestry Informative SNPs (EAIMs).

  Dataset EGAD00010000624