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• Identification of gene mutations and fusion genes in patients with Sézary Syndrome

  Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma (CTCL) with an aggressive clinical course. The goal of our study is to understand the genetic basis of the disease by looking for driver gene mutations and fusion genes in 15 erythrodermic patients with circulating Sezary cels, fourteen of them fulfilling the diagnostic criteria of SS. Peripheral blood samples were collected for each patient and CD4+ T-lymphocytes and Granulocytes were isolated. DNA and RNA was extracted for matched normal and tumor materials. Whole exome sequencing was performed on matched normal and tumor tissues of 12 patients and RNA sequencing was performed on 10 patients. For 7 of these patients, we have both exome as well as RNA sequencing data. In this study, we present a complex genomic landscape of Sezary syndrome with several point mutations, copy number variations and fusion events which could contribute to the pathogenesis of SS.

  Study EGAS00001001706

• Sequencing data from MethylScan assay on plasma

  Machine learning models in biomedical research are often hindered by demographic imbalances in clinical datasets, leading to biased predictions that disadvantage minority populations. Existing bias correction methods face limitations in handling the heterogeneity of biomedical data and the complexity of demographic influences. Here, we present DeBias, a computational framework for mitigating demographic biases in high-dimensional biomedical datasets. DeBias eliminates bias-associated subspaces within the entire feature space using control samples and enables global bias correction across all features, effectively preserving disease-specific signals while minimizing demographic distortions. To demonstrate its effectiveness, we applied DeBias to cfDNA methylation data for cancer detection. It achieved a >6-fold reduction in the number of features containing biases and outperformed existing methods in improving the cancer detection performance for minority populations. Our method represented a promising step toward developing machine learning models that are more accurate, reliable, and equitable for minority populations.

  Study EGAS00001008127

• PASCAL-MID Data Access Committee

  DAC for the center of Personalized Approach to Genome Editing of Stem Cells for Autotransplantation of Monogenic Immunodeficiencies (PASCAL-MID) at Aarhus University and Aarhus University Hospital

  Dac EGAC50000000680

• V4_Colorectal_panel_test

  Targeted gene screen of cell line tumours for testing the new V4 Colorectal gene panel.

  Study EGAS00001001807

• DATA FILES FOR SJPHALL

  DATA FILES FOR SJPHALL

  Dataset EGAD00001000163

• DATA FILES FOR GRUBER SJAMLM7 EXOME

  DATA FILES FOR GRUBER SJAMLM7 EXOME

  Dataset EGAD00001003134

• PACA-CA RNASeq fastq files

  Fastq files for PACA-CA RNA Seq analysis, for DCC release 27

  Dataset EGAD00001003972

• DATA FILES FOR BALL-PAX5

  DATA FILES FOR BALL-PAX5

  Dataset EGAD00001000654

• DATA FILES FOR SJMEL-WGS

  DATA FILES FOR SJMEL-WGS

  Dataset EGAD00001001032

• DATA FILES FOR SJTALL

  DATA FILES FOR SJTALL

  Dataset EGAD00001001052

• KiCS cancer panel academic only data

  This data set contains KiCS cancer panel data for academic and for-profit use.

  Dataset EGAD00001009733

• Dataset for B-ALL scRNA-seq

  10x Genomics 5' library scRNA-seq data for 85 B-ALL patients with different subtypes

  Dataset EGAD00001011327

• Gene Expression Signatures Characterized by Longitudinal Stability and Inter-Individual Variability Delineate Baseline Phenotypic Groups with Distinct Responses to Immune Stimulation

  RNA sequencing (RNAseq) of peripheral blood lymphocytes was used to develop a means to assess immune function in a way that can be used in discovery science and applied to patients individually in clinical settings. The premise is that profiles of RNA present in immune cells is reflective of the combined influence of genetic and environmental variation on immune potential of individuals and that this potential can be tapped to understand human immunity in a variety of biological contexts. CD4+ cells were isolated from fresh whole blood via positive magnetic bead selection and cell lysates were prepared using Qiazol (QIAGEN) and stored at -80ºC for 3 to 8 months. RNA was extracted in batches for cDNA library preparation and RNA-Seq. For this study, we developed standard operating procedures for handling human blood samples and determined: a) the best way to enrich for CD4+ T cells from whole blood and yield high quality RNA, b) the sensitivity of this RNA profiling strategy, and c) the reproducibility of generated immune profiles from healthy subjects. We then developed bioinformatics processes to establish immune response signatures and immune response phenotypes within cohorts of individuals.

  Study phs001512

• National Eye Institute (NEI) Exfoliation Genotyping Study

  The overall goal of our research is to elucidate the pathogenesis of exfoliation syndrome and the associated glaucoma, making it possible to implement effective screening and prevention strategies and to develop novel therapies. Cases genotyped for this project are from the Nurses Health Study (NHS), the Health Professionals Follow-up Study (HPFS), the Women's Genome Health Study (WGHS), the Massachusetts Eye and Ear Infirmary (MEEI), Mayo Clinic, the University of Iowa, the University of Miami and Duke University Medical Center. Exfoliation syndrome (XFS) is a common condition that is a major risk factor for high-tension open-angle glaucoma, pre-mature cataract formation, and increased risk of complications during cataract surgery. Previous studies suggest that exfoliation syndrome and the related glaucoma (XFG) are genetically complex, and one gene, LOXL1, has been identified as a major genetic risk factor. LOXL1 variants are found in up to 98% of affected patients; however, these same variants are also present in up to 80% of unaffected individuals, indicating that additional genetic and/or environmental factors are necessary for disease development. Samples genotyped for this study are a case set (1,096 samples) and 24 pedigrees (98 samples). Controls for association analyses are selected from the NEIGHBORHOOD study.

  Study phs001053

• Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants and parents), NIDDK

  Genetics of Kidneys in Diabetes (GoKinD) study is an initiative aimed at identifying susceptibility genes for diabetic nephropathy in type 1 diabetes. A large number of individuals with type 1 diabetes were screened to identify two subsets, one with clear-cut kidney disease and another with normal renal status despite long-term diabetes. Those who met additional entry criteria and consented to participate were enrolled. When possible, both parents were also enrolled to form family trios. Altogether, GoKinD includes 3043 participants comprising 931 cases, 944 singletons, 268 pairs of parents of cases, and 316 pairs of parents of control. Accessible as a GAIN database are 905 of the cases, 890 of the controls, 10 pairs of parents of cases and 10 pairs of parents of controls (dbGaP phs000018 Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants), GAIN). The other parents and the remaining cases and controls are available by a separate application process through NIDDK. Interested investigators may request the DNA collection and corresponding clinical data for GoKinD participants using the instructions and application form available at http://www.niddkrepository.org or by contacting the Juvenile Diabetes Research Foundation.

  Study phs000088

• Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

  Cancer-associated fibroblasts (CAFs) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we employ single-cell RNA-sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human PDAC tumors. Six human PDAC tumor specimens from six patients were collected, and processed for single-cell RNA-sequencing analysis. Adjacent-normal pancreas tissue was also collected from two of the patients. Tumor samples were digested, and fluorescence-activated cell sorting was used to isolate viable cells. For one tumor sample, viable, CD45-negative, CD31-negative, and EpCAM-negative cells were also isolated to enrich for CAFs. The 10X Chromium platform was then used to isolate single cells for RNA-sequencing analysis. This work has demonstrated the differences in immune cell populations between adjacent-normal and tumor tissues, and identified subpopulations of epithelial cells and CAFs present in PDAC tumors. This high-throughput analysis is a resource to better understand the cell populations present in PDAC, and may ultimately aid in the development of more effective therapies for this deadly malignancy.

  Study phs001840

• CIDR: Genome Wide Association Study in Familial Parkinson Disease (PD)

  This proposal brings together the two largest NIH funded genetic studies focused on the identification of novel genes that influence the risk of PD. These two studies, PROGENI (PI: Tatiana Foroud; R01NS037167) and GenePD (PI: Richard Myers; R01NS036711) have been evaluating and recruiting families with two or more PD affected members for more than 8 years and represent the largest such cohorts world-wide. The combined sample has more than 1,000 PD families. Each study has used rigorous clinical criteria to assess their study participants. Unlike previous genome wide association studies (GWAS) in PD, all the PD cases in this proposal have a positive family history of disease. In the vast majority of these families, the index PD case has at least one sibling with the disease. Thus, the sample is unique for having substantial evidence for a genetic contribution to disease. The control group for this study consists of samples previously collected and maintained by the NINDS Repository. Genome-wide, single nucleotide polymorphism (SNP) genotyping services were provided by the Center for Inherited Disease Research (CIDR). Data analyses will focus on the identification of SNPs associated with PD susceptibility and the age of onset of disease.

  Study phs000126

• Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants), GAIN

  Genetics of Kidneys in Diabetes (GoKinD) study is an initiative aimed at identifying susceptibility genes for diabetic nephropathy in type 1 diabetes. A large number of individuals with type 1 diabetes were screened to identify two subsets, one with clear-cut kidney disease and another with normal renal status despite long-term diabetes. Those who met additional entry criteria and consented to participate were enrolled. When possible, both parents were also enrolled to form family trios. Altogether, GoKinD includes 3043 participants comprising 931 cases, 944 singletons, 268 pairs of parents of cases, and 316 pairs of parents of control. Accessible as a GAIN database are 905 of the cases, 890 of the controls, 10 pairs of parents of cases and 10 pairs of parents of controls. The other parents and the remaining cases and controls are available by a separate application process through NIDDK (dbGaP phs000088 Search for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes (GoKinD study participants and parents), NIDDK). Interested investigators may request the DNA collection and corresponding clinical data for GoKinD participants using the instructions and application form available at Juvenile Diabetes Research Foundation. Consent groups and participant set Diabetic complications only (DCO): 1825 (904 cases, 881 controls, 40 others)

  Study phs000018

• DEMENTIA-SEQ: WGS in Lewy Body Dementia and Frontotemporal Dementia

  Lewy body dementia, amyotrophic lateral sclerosis/frontotemporal dementia, and multiple system atrophy are age-related, neurodegenerative syndromes that are poorly understood. Delineating the genetic risk that is driving the pathophysiology of these neurological diseases is fundamental for understanding disease mechanisms and for developing disease-modifying treatments. In version 1 of the study/dbGaP deposition, we performed a whole-genome sequencing study consisting of 7,403 total samples, including 2,633 genomes from patients with Lewy body dementia, 2,641 frontotemporal dementia patients, and 1,980 neurologically healthy controls. Of these, 6,907 were uploaded to dbGaP as the basis of the DementiaSeq, phs001963 dataset. The data relating to these samples are available on dbGaP. In version 2 of this study/dbGaP deposition, we made much of these data available on Anvil. More specifically, data for 6,254 of these samples were also uploaded to the ALS Compute platform on AnVIL. The data for the remaining 653 samples are only available on dbGaP. The dbGaP/AnVIL Table lists the availability of dbGaP and AnVIL for each individual sample: phd008475.In version 3 of the study/dbGaP deposition, we added whole-genome sequence data generated using DNA samples obtained from 683 patients diagnosed with multiple system atrophy.

  Study phs001963

• Unifying recovery dynamics in heterogeneous diseases exemplified by COVID-19

  Studying the recovery dynamics in different diseases poses many difficulties, as patients often display high heterogeneity in their recovery courses. Moreover, most attempts to study disease dynamics focus on disease progression rather than disease recovery mechanisms. To model recovery dynamics, using severe COVID-19 as the example, we align heterogeneous recovery trajectories via a novel computational scheme applied to longitudinally sampled blood transcriptomes. We thus generate pseudotime trajectories, which we then link to cellular and molecular mechanisms based on cell deconvolution analysis and molecular pathway prediction, thus presenting a unique framework for studying recovery processes over time. Specifically, mature neutrophils displayed a gradual decrease during recovery, allowing superior useability for outcome prediction compared to currently used clinical markers. Further, we discovered a recovery-related regulatory change in gene programs resulting in immune rebalancing between interferon and NFkB activity and the restoration of cell homeostasis. We thus propose regulatory mechanisms governing COVID-19 recovery and suggest mature neutrophils and additional gene markers, as novel clinical biomarkers for disease outcome. Overall, we present a novel clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.

  Study EGAS00001005735

• Cardiovascular disease biomarkers derived from circulating cell-free DNA methylation

  Acute coronary syndrome (ACS) remains a major cause of worldwide mortality. The syndrome occurs when blood flow to the heart muscle is decreased or blocked, causing muscle tissues to die or malfunction. There are three main types of ACS: Non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina. The treatment depends on the type of ACS, and this is decided by a combination of clinical findings, such as electrocardiogram and plasma biomarkers. Circulating cell-free DNA (ccfDNA) is proposed as an additional marker for ACS since the damaged tissues can release DNA to the bloodstream. We used ccfDNA methylation profiles for differentiating between the ACS types and provided computational tools to repeat similar analysis for other diseases. We leveraged cell type specificity of DNA methylation to deconvolute the ccfDNA cell types of origin and to find methylation-based biomarkers that stratify patients. We identified hundreds of methylation markers associated with ACS types and validated them in an independent cohort. Many such markers were associated with genes involved in cardiovascular conditions and inflammation. ccfDNA methylation showed promise as a non-invasive diagnostic for acute coronary events. These methods are not limited to acute events, and may be used for chronic cardiovascular diseases as well.

  Study EGAS00001007263

• Botswana 15 autosomal unlinked microsatellites

  Population structure was investigated in 990 Botswana individuals according to ethno-linguistics, Bantu and Khoisan, and geography (the nine administrative districts) using the AmpFLSTR Identifiler autosomal microsatellite markers. Genetic diversity and forensic parameters were calculated for the overall population, and according to ethno-linguistics and geography. The overall combined power of exclusion (CPE) was 0.9999965412 and the combined match probability 6,28 x 10-19. CPE was highest for the Khoisan Tuu ethnolinguistic group and the Northeast District at 0.9999582029 and 0.9999922652 respectively. CMP ranged from 6.28 x 10-19 (Khoisan Tuu) to 1,02 x 10-18 (Northwest district). Using pairwise genetic distances (FST), analysis of molecular variance (AMOVA), factorial correspondence analysis (FCA), and the unsupervised Bayesian clustering method found in STRUCTURE and landscape genetics software TESS, ethno-linguistics were found to have a greater influence on population structure than geography. FCA showed clustering between Bantu and Khoisan, and within the Bantu. This Bantu sub-structuring was not seen with STRUCTURE and TESS, which detected clustering only between Bantu and Khoisan. The patterns of population structure revealed highlight the need for regional reference databases that include ethno-linguistic and geographic location information. These markers have important potential for bio-anthropological studies as well as for forensic applications.

  Study EGAS00001002380

• Whole exome sequencing on primary retinoblastoma tissues and matching lymphocyte DNA.

  Retinoblastoma is a rare childhood cancer initiated by RB1 mutation or MYCN amplification, while additional alterations may be required for tumor development. However, the view on single nucleotide variants is very limited. To better understand oncogenesis, we determined the genomic landscape of retinoblastoma. We performed exome sequencing of 71 retinoblastomas and matched blood DNA. Next, we determined the presence of single nucleotide variants, copy number alterations and viruses. Aside from RB1, recurrent gene mutations were very rare. Only a limited fraction of tumors showed BCOR (7/71, 10%) or CREBBP alterations (3/71, 4%). No evidence was found for the presence of viruses. Instead, specific somatic copy number alterations were more common, particularly in patients diagnosed at later age. Recurrent alterations of chromosomal arms often involved less than one copy, also in highly pure tumor samples, suggesting within-tumor heterogeneity. Our results show that retinoblastoma is among the least mutated cancers and signify the extreme sensitivity of the childhood retina for RB1 loss. We hypothesize that retinoblastomas arising later in retinal development benefit more from subclonal secondary alterations and therefore, these alterations are more selected for in these tumors. Targeted therapy based on these subclonal events might be insufficient for complete tumor control.

  Study EGAS00001001690

• Host pathogen interaction long read transcriptome

  Our incomplete knowledge of the human transcriptome impairs the detection of disease-causing variants, in particular in transcripts only expressed under certain conditions. These transcripts are often lacking from reference transcript sets, such as Ensembl/GENCODE and RefSeq, and could be relevant for establishing genetic diagnoses. We present SUsPECT (Solving Unsolved Patient Exomes/gEnomes using Custom Transcriptomes), a pipeline based on the Ensembl Variant Effect Predictor (VEP) to predict variant impact on custom transcript sets, such as those generated by long-read RNA-sequencing, for downstream prioritization. Our pipeline predicts the functional consequence and likely deleteriousness scores for missense variants in the context of novel open reading frames predicted from any transcriptome. We demonstrate the utility of SUsPECT by uncovering potential mutational mechanisms of pathogenic variants in ClinVar that are predicted to be benign using the reference transcript annotation. In further support of SUsPECT’s utility, we identified an enrichment of immune-related variants predicted to have a more severe molecular consequence when annotating with a newly generated transcriptome from stimulated immune cells instead of the reference transcriptome. Our pipeline outputs crucial information for further prioritization of potentially disease-causing variants for any disease and will become increasingly useful as more long-read RNA sequencing datasets become available.

  Study EGAS00001006779

• Integrative Multi-Omics and Drug Sensitivity Profiling Reveals Potential Predictive Biomarkers in Pediatric Solid Tumors from the INFORM Registry

  Cure rates for childhood malignancies using established therapy protocols have increased to an average of 80% but have reached a plateau. Moreover, survival rates are particularly low for some pediatric tumors (such as high-risk Group3 medulloblastomas, osteosarcomas, Ewing sarcomas, high-risk neuroblastomas and high-grade gliomas) and dismal for patients with relapsed malignancies. A functional drug response profiling platform for pediatric solid and brain tumors has been established within the INFORM program to identify patient-specific vulnerabilities, biomarkers and unravel molecular mechanisms associated with drug response profiles for clinical translation. Here, we perform a multi-omics analysis using drug sensitivity profiles, genomic, and transcriptomic data of 81 pediatric solid tumor samples. The integrative analysis revealed two multi-omics signatures with high drug sensitivity predictivity. One signature highlighted neuroblastoma samples with sensitivity to navitoclax (a BCL-2 family inhibitor). A second signature was significantly specific to a subset of Wilms tumors harboring the SIX1 (Q177R) hotspot mutation, which had high expression of MGAM, PTPN14, STAT4 and KDM2B and high sensitivity to MEK inhibitors. A patient-specific causal interaction network analysis elucidated the potential biological mechanism of action between MEK inhibitors and the SIX1 mutation in n = 6 Wilms tumor samples.

  Study EGAS00001008249

• Identification of biomarkers of response to preoperative talazoparib monotherapy in treatment naïve gBRCA+ breast cancers

  Germline mutations in BRCA1 or BRCA2 exist in ~2-7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting. We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%. As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance. To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib. We looked for biomarkers that were predictive of response (assessed by residual cancer burden) after 6 months of therapy. We found that all resistant tumors exhibited either the loss of SHLD2, expression of a hypoxia signature, or expression of a stem cell signature. These results indicate that the deep analysis of pre-treatment tumors can identify biomarkers that are predictive of response to talazoparib and potentially other PARP inhibitors, and provides a framework that will allow for better selection of patients for treatment, as well as a roadmap for the development of novel combination therapies to prevent emergence of resistance.

  Study EGAS00001005676

• WTCCC case-control study for Rheumatoid Arthritis - Combined Controls

  WTCCC genome-wide case-control association study for Rheumatoid Arthritis (RA) using six disease collections together with the 1958 British Birth Cohort and the UK National Blood Service collections as controls.

  Study EGAS00000000012

• WTCCC case-control study for Bipolar Disorder

  WTCCC genome-wide case-control association study for Bipolar disorder (BD) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.

  Study EGAS00000000001

• BLUEPRINT ATAC-seq data for cells in the haematopoietic lineages, from adult and cord blood samples

  BLLUEPRINT ATAC-seq data for cells in the haematopoietic lineages, from adult and cord blood samples.

  Study EGAS00001001596

• RNAseq of liver harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 or vehicle

  This experiment consists of RNAseq of liver harvested from CDAHFD mice treated for 8 weeks with either the MGAT2 inhibitor compound BMS-963272 (N = 10) or with vehicle (N = 10).

  Study EGAS00001006583

• RNA sequencing of baseline HCC PDX models

  To establish the baseline transcriptional profiles, we performed bulk RNA-seq for 36 of our HCC PDX models. 2-6 samples were collected for each model resulting in a total of 68 samples. Isolated RNA was used as input for library preparation using TruSeq RNA Sample Preparation Kit v2 (Illumina). The libraries were multiplexed and sequenced on Illumina HiSeq 2500 (Illumina) to produce FASTQ files.

  Dataset EGAD50000000736

• ESGI - Molecular diagnosis for mitochondrial disorders (2017-08-29)

  The MITOEXME project aims to improve protocols for molecular diagnosis of patients with OXPHOS disorders with a focus on a next generation sequencing methods and to increase the knowledge of pahtophysiological mechanisms by identification of new targets and cellular studies. In this project we will sequence the exomes fo 120 patients. This dataset contains all the data available for this study on 2017-08-29.

  Dataset EGAD00001003596

• Paired-end Whole Exome-seq analysis of multi-centric lower grade glioma

  This dataset includes Nimblegen SeqCap EZ Exome v3 data for each lesion of three patients with multicentric glioma. For two patients, each lesion was sequenced along with whole blood. For a third patient, 3 pieces from the right lesion and 4 pieces from the left were sequenced along with whole blood. In each case BAM files that have been aligned with BWA mem alignment are available.

  Dataset EGAD00001003795

• RNA-Seq of novel miR (nmiR-1 and nmiR-2) overexpression and knockdown in BL

  After overexpression and knockdown of both described novel miRs nmiR-1 and nmiR-2 in BL cell lines (SU-DHL4 for nmiR-1 and Raji for nmiR-2), we performed regular RNA-Seq (including Mock controls for all cell lines) to identify their direct and indirect downstream mRNA targets.

  Dataset EGAD00001001612

• BLUEPRINT WP10 Quantitative Trait Loci (QTLs) Phase 2 Full Summary Statistics

  BLUEPRINT WP10 Quantitative Trait Loci (QTLs) Phase 2 full summary statistics data include five molecular traits (eQTL, hQTL(H3K27ac), hQTL(H3K4me1), mQTL, and psiQTL) for three primary blood cells (Monocytes, Neutrophils, and T-cells). Each full summary statistics file contains the associations for all tested variants for each phenotype ID.

  Dataset EGAD00001005199

• Reference single cell SNP array dataset from Coriell for training and validation of method for accurate single cell genotyping

  This dataset contains DNA from B-lymphocytes from 2 Coriell families and 4 individuals hybridized to HumanKaryomap BeadChip Array. Single cells from subjects GM12878 and GM7228 were amplified using multiple displacement amplification (SureMDA) according to Infium Karyomapping Assay Guide. Bulk DNA was processed and hybridized to an array for subject GM12878, GM07224 and GM07225.

  Dataset EGAD00001006376

• WES and WGS data for HGSC patient derived cell lines and fresh frozen tumor samples from same patients

  Sequencing data for three HGSC patients with patient derived cell lines. WES data for two patient derived cell line samples and matched blood control samples. Fresh frozen tumor samples of two patients with WES or WGS sequencing data.

  Dataset EGAD00001009330

• DAC for TFHL single-cell analysis project at Department of Hematology, University of Tsukuba

  DAC for study of tumor heterogeneity and immune-evasive microenvironment in T follicular helper cell lymphomas

  Dac EGAC50000000201

• Pancreatic Cancer NGS WGS data

  Whole genome sequencing data for Pancreatic Cancer Samples exploring the tandem duplicator phenotype

  Study EGAS50000001078

• Additional Methylation files for Roussel-ATRT-TM

  Additional Methylation files for Roussel-ATRT-TM paper titled "Atypical teratoid/ rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities"

  Dataset EGAD00010002495

• Array data for oesophageal and related samples – kno_paper_methyl_release

  Array data for oesophageal and related samples – kno_paper_methyl_release

  Dataset EGAD00010001795

• Targeted sequencing analysis for MDS with HSCT

  Targeted capture sequencing for cases with MDS who were subjected to unrelated bone marrow transplantation via Japan marrow donor program

  Dataset EGAD00001003118

• Data files for CONSERTING

  Data files for CONSERTING (WGS)

  Dataset EGAD00001001352

• DATA FILES FOR PCGP SJINF WES

  DATA FILES FOR PCGP SJINF WES

  Dataset EGAD00001001245

• National Eye Institute (NEI) Age-Related Eye Disease Study (AREDS)

  The Age-Related Eye Disease Study (AREDS) was initially designed as a long-term multi-center, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. In addition to collecting natural history data, AREDS included a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. AREDS participants were 55 to 80 years of age at enrollment and had to be free of any illness or condition that would make long-term follow-up or compliance with study medications unlikely or difficult. On the basis of fundus photographs graded by a central reading center, best-corrected visual acuity and ophthalmologic evaluations, 4,757 participants were enrolled in one of several AMD categories, including persons with no AMD. The clinical trials for AMD and cataract were conducted concurrently. AREDS participants were followed on the clinical trials for a median time of 6.5 years. Subsequent to the conclusion of the clinical trials, participants were followed for an additional 5 years and natural history data were collected. The AREDS research design is detailed in AREDS Report 1. AREDS Report 8 contains the mainline results from the AMD trial; AREDS Report 9 contains the results of the cataract trial. Blood samples were also collected from 3,700+ AREDS participants for genetic research. Genetic samples from 600 AREDS participants (200 controls, 200 Neovascular AMD cases, and 200 Geographic Atrophy cases) were selected using data available in March 2005 and then were evaluated with a genome-wide scan. These data, as well as selected phenotypic data, were made available in the dbGaP. DNA from AREDS participants, which is currently being stored in the AREDS Genetic Repository, is available for research purposes. However, not all of the 3,700+ AREDS participants who submitted a blood sample currently have DNA available. In addition to including the data from the genome-wide scan on the 600 original samples, this second version of the AREDS dbGaP database provides a comprehensive set of data tables with extensive clinical information collected for the 4,757 participants who participated in AREDS. The tables include information collected at enrollment/baseline, during study follow-up, fundus and lens pathology, nutritional estimates, quality of life measures and measures of morbidity and mortality. In November 2010, over 72,000 high quality fundus and lens photographs of 595 AREDS participants (of the original 600 selected for the genome-wide scan) were made available in the AREDS dbGaP. In addition to the genome-wide scan data, the fundus and lens grading data for these participants are also available through the AREDS dbGaP. Details about the ocular photographs that are available may be found in the document "Age-Related Eye Disease Study (AREDS) Ocular Photographs". In January 2012, a measure of daily sunlight exposure was added in a separate "sunlight" table. Furthermore, the "followup" table has been revised. The visual acuity for the right eye was inadvertently missing at odd-numbered visits (01, 03, 05, etc.). This data is now part of the table. In February 2014 over 134,500 high-quality fundus photographs (macular field F2) of 4613 AREDS participants were added to the existing AREDS dbGaP resource. The AREDS dbGaP image archive already contains over 72,000 high quality fundus and lens photographs of 595 AREDS participants for whom dbGaP-accessible genotype data exist. Information about the available ocular photographs found in the document "Age-Related Eye Disease Study (AREDS) Ocular Photographs" has been updated with an addendum. It is hoped that this resource will better help researchers understand two important diseases that affect an aging population. These data may be applied to examination and inference on genetic and genetic-environmental bases for age-related diseases of public health significance and may also help elucidate the clinical course of both conditions, generate hypotheses, and aid in the design of clinical trials of preventive interventions. Definitions of Final AMD Phenotype Categories Please see phd001138.1 for a detailed description of how AREDS participants' final AMD phenotype was categorized. User's Guide for AREDS Phenotype Data A detailed User's Guide for the AREDS phenotype data is available. This User's Guide is meant to be a comprehensive document which explains the complexities of the AREDS data. It is recommended that all researchers using AREDS phenotype data make use of this User's Guide.

  Study phs000001

• NHLBI TOPMed: Defining the Time-Dependent Genetic and Transcriptomic Responses to Cardiac Injury Among Patients with Arrhythmias

  The UMMS miRhythm Study is an ongoing study of adult patients undergoing an elective electrophysiology study or arrhythmia ablation procedure for a supraventricular or ventricular arrhythmia, including atrial fibrillation (AF). Atrial fibrillation is a major clinical and public health problem that is related to atrial pathologic remodeling. Few tools are available to quantify the activity or extent of this remodeling, rendering it difficult to identify individuals at risk for AF. Previous studies have suggested an important role for miRNA in cardiovascular disease through gene expression regulation, making this a promising avenue for studying AF mechanisms. The aim of the study is to determine the time-dependent changes to key circulating miRNAs in a model of planned atrial injury and remodeling via ablation. Such knowledge might provide additional insight into the biology and activity of the acute atrial injury response, and furthermore, inform new targets for development of preventative interventions or allow for better AF risk stratification. To assess pathways regulating atrial pathological remodeling, patient blood samples are collected prior to their ablation procedures and also at a regularly scheduled 1-month follow-up appointment. Plasma expression of miRNA is measured using high-throughput quantitative reverse transcriptase polymerase chain reaction (RT-qPCR), providing novel insights into the regulatory processes underlying AF, as well as acute atrial injury in vivo. Additionally, data collected from whole-genome sequencing (WGS) is used to supplement miRNA analyses and further explore new relations between genes and abnormal heart rhythm.

  Study phs001434

• Methylation differences in trisomy 21 using monozygotic twins

  We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in T21. In order to determine the methylation differences in T21 without the interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. We applied Reduced Representation Bisulfite Sequencing (RRBS) to generate genome wide nucleotide resolution of DNA methylation based on high throughput sequencing between each pair of samples. RRBS revealed differentially methylated promoter regions (DMRs) in MZ twins discordant for T21 that have also been observed in unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) in the iPSC of the T21 versus normal twin. Additionally, two sets of T21 MZ twins discordant for heart defect highlighted DMRs in genes that are associated with heart development. In conclusion the study of DNA methylation differences in MZ twins discordant for genomic abnormalities is a promising approach to understand the molecular pathophysiology of aneuploidies.

  Study EGAS00001001051

• Comparison of the diagnostic yield of aCGH and NGS across different neurodevelopmental disorders

  Current recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). The present study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: Global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and Other NDDs. These categories were further subclassified into subcategories, based on the most frequent accompanying signs and symptoms: isolated forms, forms with epilepsy; forms with micro or macrocephaly and syndromic forms. A subset of 245 patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results support the use of NGS as the first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.

  Study EGAS00001004949

• Transcriptome_human_nasal_epithelium

  1. Odors are detected, firstly, by olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose. This neurons then project directly to the olfactory bulb in the brain. Olfaction depends on cellular regeneration of the OE, olfactory bulb and hippocampus, and on their continual re-wiring. The olfactory neural pathway includes regions of the frontal, temporal and limbic brain, which in turn overlap with brain areas involved in brain disorders. OSNs are the only aspect of the human brain exposed to the external environment. This not only makes them vulnerable to environmental changes, but also accessible for biomedical studies.We have already sequenced and developed a protocol for analyzing the transcriptome of mouse main olfactory epithelium and single OSNs. We propose here to perform a similar study for samples from the human olfactory epithelium. We have developed a minimally invasive method for obtaining human OSNs, among other cells from the nasal epithelium. In this experiment, we have obtained cell samples from the olfactory epithelium, including OSN, from healthy volunteers. We would like to further characterize them by RNA sequencing. This will give us valuable insight into human olfaction. It will also provide a first step into a new avenue to study, and find biomarkers for, brain diseases though the analysis of these easily available neurons. 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 EGAS00001001294

• Phylogenetic analysis of treatment-naive metastases using whole exome and genome sequencing data

  Metastases are responsible for the majority of cancer related deaths and are often difficult to treat successfully. Even for metastases that occur subsequent to treatment, we do not know whether such relapsing metastases were originally heterogeneous or if the observed heterogeneity is a consequence of therapy. Given that treatment can influence evolutionary dynamics by selecting resistant clones, imposing bottlenecks on cancer cell populations, and even inducing novel somatic mutations, characterizing the prior standing variation among metastases remains an important goal to predict initial therapeutic response. To quantify the heterogeneity at clinical presentation of advanced disease, we surveyed the literature for patients in which at least two treatment-naïve metastases underwent genome/exome-wide sequencing. Across all cancer types surveyed, only 18 subjects were found to fulfill this requirement. Including previously unpublished data from two subjects, we analyzed data of 74 untreated metastases and inferred cancer phylogenies. Putative driver gene mutations were acquired at a 2-fold higher rate on the trunk of all metastases than on branches. Mutations in driver genes along the trunk were strongly enriched for predicted functional consequences. Using a stochastic mathematical model, we find that driver gene heterogeneity among metastases mostly occurs in slowly growing cancers for highly advantageous driver gene mutations. Seeding efficiency only weakly affects the heterogeneity among metastases. These results explain why functional driver gene heterogeneity is uncommon in advanced disease prior to treatment, thus providing optimism for future therapies that depend on mutations across metastases.

  Study EGAS00001002777

• Transcriptome Sequencing PPGL

  RNA library preparation of samples with RNA Integrity Number (RIN) > 5.5 (median 7.1; range 5.6-8.9) was performed as described in the TruSeq Stranded mRNA Library Prep Kit (Illumina, RS-122-2101). Briefly, 0.7-1 µg total RNA PolyA+ fraction was purified and randomly fragmented, converted to double stranded cDNA and processed through subsequent enzymatic treatments of end-repair, dA-tailing, and ligation to adapters. Adapter-ligated library was completed by PCR with Illumina PE primers. The resulting purified cDNA library was applied to an Illumina flow cell for cluster generation and sequenced on an Illumina HiSeq2500 on a 51bp single-read format following manufacturer's protocols. cDNA libraries from FFPE tumors and low integrity RNA’s (RIN<5.5) from FF tumors (median 2.4; range 1-5.5) but % of fragments > 200 nucleotides higher than 20% (median 57.5; range 20-96) were prepared using QuantSeq 3’ mRNA-Seq Library Prep Kit FWD for Illumina (Lexogen, 015) with a UMI Second Strand Synthesis Module for QuantSeq FWD (Lexogen, 081), vendor’s protocol for low input/ low quality/ FFPE RNA using 200-500 ng of total RNA, according to availability, was used as starting material. PCR Add-on Kit for Illumina (Lexogen, 020) was used to adjust the library amplification number of cycles. Libraries were applied to an Illumina flow cell for cluster generation and sequenced on NovaSeq6000. Image analysis, per-cycle basecalling and quality score assignment was performed with Illumina Real Time Analysis software. Demultiplexing of BCL files to FASTQ format was performed with the bcl2fastq Software (Illumina).

  Study EGAS00001006044

• Analysis of the Elements Involved in the Enrichment of a Panel of Genomic Regions by Nanopore Sequencing Using Adaptive Sampling

  DNA sequencing using nanopore technologies with the affordable MinION device is useful for the identification and characterization of structural variants, long haplotypes, sequencing of repetitive regions and identification of epigenetic modifications. The main limitation of this approach is the low coverage obtained, which might be avoided by adaptive sampling, a computationally controlled method of enrichment for targeted genomic regions. This study dissects the factors involved in the enrichment by adaptive sampling of a panel of 18 human genome regions containing 20 genes implicated in breast cancer sequenced in 16 patients with familial breast cancer negative for NGS screening. An average coverage of 2.0x was obtained for the whole genome and 5.1x for selected regions. Sequencing time was the main factor improving coverage. The selection of long reads (>1 Kb) did not improve the enrichment. The length of the selected region, which in our study ranged from 126 to 565 Kb, did not play a significant role in enrichment. However, the region containing PMS2 showed significantly lower coverage, which could be explained by the high number of PMS2 pseudogenes (N = 14), which were also enriched. Our study shows new evidence of enrichment obtained by adaptive sampling in a panel of genomic regions and shows parameters, the relevance of sequencing time and the role of pseudogenes, that improve the enrichment yield with no library reloading or GPU use, data useful for a more efficient application of this procedure in future studies.

  Study EGAS00001007375

• 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

• Uncovering RNA Signatures of C9orf72-Linked ALS and Related Disorders

  Substantial clinical and pathological variability has been reported in patients carrying an expanded repeat in C9orf72, who are generally diagnosed with amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). Emerging evidence suggests that C9orf72 expression, RNA foci, and dipeptide-repeat proteins contribute to C9orf72-related diseases; however, the majority of the clinicopathological variability remains unexplained. We hypothesize that RNA sequencing (RNA-Seq) might reveal individual genes or groups of highly correlated genes (modules) that could account for this variability, which may help to identify much-needed druggable targets and/or biomarkers. Our preliminary studies performed in the frontal cortex, where we compared C9orf72 expansion carriers to (disease) controls, demonstrated that the top differentially expressed gene was C9orf72 itself. We also noticed that differentially expressed genes were enriched for the endocytosis pathway, which is consistent with the reported function of the C9orf72 protein in vesicle trafficking. Furthermore, we detected a module enriched for vesicular pathways, and additionally, we discovered an association with survival after onset for several promising candidates involved in vesicular transport. To find new therapeutic targets and biomarkers, here we have completed RNA-Seq on an increased number of samples to examine another relevant region: the cerebellum. As such, we performed RNA-Seq on a well-characterized cohort of C9orf72 expansion carriers, patients without this expansion, and control subjects without neurological diseases. We used multivariable linear regression models for gene-level analysis, weighted correlation network analysis for module-level analysis, and leafcutter for splicing analysis. Using the cerebellar RNA-Seq data, we found a large number (>6,000) of differentially expressed genes, with a notable increase in expression of homeobox genes in C9orf72 expansion carriers, as well as many gene modules that were associated with C9orf72 expansion status. Additionally, using leafcutter, we detected over 1,000 differential splicing events and an increase in the number of cryptic splicing events in C9orf72 expansion carriers.

  Study phs003065

• The Sea Islands Genetic Network (SIGNET): Identifying genetic contributors to diabetes and dyslipidemia in African Americans

  Recent genome-wide association studies (GWAS) have successfully identified genetic variants that influence diabetes risk in European populations, however most do not have a major impact on diabetes risk in populations of African descent. The African American (AA) population from the Sea Islands of coastal South Carolina and Georgia has high rates of type 2 diabetes, low levels of admixture, and in general, consume a diet rich in saturated fats. We postulate that this unique combination of ancestral and environmental factors results in a more consistent penetrance of diabetes risk alleles, as well as enrichment of risk alleles of African origin. The existing DNA samples and rich phenotypic data from the Sea Island Families Project comprise a unique resource for genetic studies of type 2 diabetes and related metabolic traits such as dyslipidemia. Our central hypothesis is that the increased risk for T2DM in AA compared with European American (EA) is due, in part, to susceptibility alleles of African origin, and that these alleles can be identified using a GWAS. The Specific Aims are to: 1) Identify genetic risk factors for type 2 diabetes utilizing DNA samples and data from the Sea Island Families Project, Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study recruited from SC, GA, NC, and AL; and a GWAS approach; 2) Identify genetic contributors to lipoprotein subclasses in African Americans using the lipoprotein subclass profile (particle size and concentration for multiple subclasses of VLDL, LDL, and HDL) assessed by NMR at LipoScience, Inc., and the GWAS data from Aim 1. The rationale for this project is that identification and validation of novel pathophysiological pathways and informed selection of candidate genes for diabetes risk will inform development of new, targeted prevention and treatment strategies in this underserved, high risk population.

  Study phs000433

• A Phase 2 Study of Tipifarnib in Large Granular Lymphocyte (LGL) Leukemia

  LGL leukemia can be divided into three subsets including the following: αβ or γδT-LGL and NK-LGL leukemia. All three subtypes will be enrolled using a two-stage design. The primary endpoint of the study is assessment of overall clinical response. Correlative laboratory studies will be performed aimed at determining the mechanism of response to treatment. Thirteen participants will be accrued in the first stage at a dose of 300 mg BID administered intermittently every other week (i.e., 7 days on and 7 days off). If there are two or more responders, the protocol will be extended to a second stage of the study and accrual will be extended to 25 evaluable participants. Allowing for 10% rate of ineligibility due to unexpected events and dropout, we will accrue 14 patients in the first stage and 27 patients in total. Participants that withdraw from the study for reason unrelated to toxicity, will be replaced. There are two potential stopping rules for toxicity. If 3 or more participants out of the 13 enrolled in the first stage experiences grade IV neurotoxicity, the study will be stopped due to excessive toxicity. Dose reductions have been incorporated for hematologic toxicity. Treatment of T and NK LGL leukemia with immunosuppressive agents such as low-dose methotrexate generally require from four to six months for a clinical response and sometimes much longer. Therefore, in participants who show clinical improvement with less than grade three toxicity, tipifarnib treatment will be continued for as many as four additional months (12 months total). After the first 8 months, response will be assessed. The protocol treatment will be discontinued in participants with progression of disease. A long-term follow up will be performed for five years in patients that receive a complete clinical response. The long-term follow up will consist of vital signs, weight, CBCs, serum chemistries, and physical examination at six month intervals.

  Study phs000594

• Genome-wide Association Study of Myasthenia Gravis

  The purpose of this project was to conduct a genome-wide associate study to search for the genetic factors that predispose to myasthenia gravis. The rationale for this study lies in the fact that, although the immunological and physiological processes affecting the neuromuscular junctions of myasthenia gravis patients are well understood, the spectrum of genetic factors that predispose to myasthenia gravis and influence its disease manifestations are not well known. Identification of the myasthenia gravis-related genes will shed light on the fundamental cellular events underlying myasthenia gravis, and will provide focus for research aimed at developing therapies that alter the natural course of the disease. A consortium of fourteen institutions in North America collected DNA samples from 1028 people diagnosed with autoimmune myasthenia gravis. Relevant clinical data have been collected for each patient, including age of onset, severity of disease, response to drug therapy, personal and family history of other autoimmune diseases. Genotyping of the case cohort was performed in the Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD. Genotyping of the case cohort was performed using the HumanOmniExpress-12v1_C SNP array manufactured by Illumina Inc. For the control cohort, we downloaded genotype data from dbGAP (accession phs000196.v2.p1) for 1,998 US neurologically normal individuals. The control cohort had been previously genotyped at the Center for Inherited Disease Research at Johns Hopkins University on HumanOmni1-Quad version 1.0B beadchips (Illumina) as part of the NeuroGenetics Research Consortium GWAS of Parkinson's disease. Analyses were confined to the 677,673 autosomal SNPs that were common to both chips. Of the 1028 samples which were genotyped, 21 samples were excluded due to mismatched genders, 9 were excluded due to low genotype call rate, 5 samples were excluded as duplicates, and 25 samples were excluded as ethnic outliers. The remaining 972 samples were used in analysis.

  Study phs000726

• Structure and Diversity of Urinary Cell-Free DNA Informative of Host-Pathogen Interactions in Human Urinary Tract Infection

  The risk of acquiring urinary tract infection (UTI) is very high for patients who have received kidney transplants; nearly half will develop bacteriuria and an eighth viruria via BK polyomavirus in the first three years following transplantation. Current methodology for diagnosing viral and bacterial infections, while well practiced, is often limited in scope. The advent of next generation sequencing of cell-free DNA has shown promise in its ability to capture multiple perspectives of human health from discovering the origin of cell-free DNA in plasma; such a diagnostic has not been readily applied to urinary cell-free DNA. In this study, we selected 141 urine samples from a cohort of kidney transplant patients, which were collected and stored at Weill Cornell Medical College - New York Presbyterian Hospital. Of these samples, 43 samples were determined to be culture positive (> 10,000 CFU) for one or more bacterial species, including E. coli, Enterococcus, Klebsiella, Haemophilus, and Raoultella. A separate 23 samples were confirmed for BK virus nephropathy, with presence of BK polyomavirus confirmed via qPCR. We also included 29 samples from 14 patients who did not develop UTIs in the first three months following transplantation, and 11 samples that were negative for BK virus nephropathy. For a full description of samples, please see the Supplementary Data 1 in https://pubmed.ncbi.nlm.nih.gov/29925834/. From these urine samples, we aimed to capture and sequence urinary cell-free DNA using a single-stranded library preparation. In addition, we performed whole-genome bisulfite sequencing to 170 plasma samples collected from 27 hematopoietic cell transplant patients who developed graft-versus host disease and BK polyomavirus infection. We also performed Sample-Intrinsic microbial DNA Found by Tagging and sequencing (SIFT-seq) on 196 cell-free DNA (cfDNA) samples (154 plasma and 42 urine) collected from five groups of subjects. For a full description of samples, please see publications in PMID: 35864089 and PMID: 35058359.

  Study phs001564

• OurHealth - Cardiovascular Disease in South Asians

  The OurHealth Study aims to build a biobank comprised of South Asian samples from participants residing in the United States. Primary objectives are to (1) identify genetic and non-genetic drivers of cardiometabolic disease in South Asians, (2) engage participants and researchers in scientific advances and research opportunities to accelerate discovery, and (3) assess the impact of returning polygenic risk scores for cardiovascular-related health conditions. Participants use a web-based platform to complete electronic informed consent, and contribute data via (1) online health surveys, (2) mailed saliva biospecimens for sequencing, and (3) optional electronic health record sharing. Surveys capture medical history, medication data, lifestyle factors, family history, mental health history, and detailed information about cultural and ancestral background. Biospecimens, procured via saliva self-collection kits, undergo DNA isolation and are sequenced using the "blended genome exome" (BGE) method, which consists of sequencing on the NovaSeqX 10B Flowcell followed by Dynamic Read Analysis for GENomics (DRAGEN) analysis for alignment to GRCh38, mapping, and variant calling. BGE uses low-coverage whole genome sequencing (lcWGS) (2-3x) combined with deep-coverage exome sequencing (30-40x), improving on SNP arrays for common variant imputation across European and non-European populations while also capturing rare coding variants. Relative to array genotyping, coverage, genotyping breadth, imputation generalizability, and cost are more optimal.BGE requires imputation for which the NHLBI TOPMed reference panel was used, and GLIMPSE2 was used for imputation emitting genotyping dosages (i.e., 0-2 multimodal continuous). Quality control (QC) included the following procedures. Sample QC excluded those with mean coverage 3% contamination from FREEMIX/VerifyBamID, sex aneuploidy and genotype/phenotype sex-mismatch due to potential phenotyping errors, fingerprinting discordance, and sample metric-level outliers were ancestry-aware, given expected distribution differences. Variant QC metrics including allele frequencies, imputation INFO scores, and Hardy-Weinberg Equilibrium (HWE) p-values are provided with the data; the genotype files provided are not filtered.

  Study phs003821

• Prevention and Early Treatment of Acute Lung Injury (PETAL) - Low Tidal Volume Universal Support Feasibility of Recruitment for Interventional Trial (LOTUS FRUIT) (PETAL-LOTUS FRUIT-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. Objectives: The two main goals of PETAL-LOTUS FRUIT were to conduct a prospective, observational study within all PETAL Network sites to determine the frequency of and outcomes from acute respiratory failure and the current usual care for tidal volume ventilation in patients with and without acute respiratory distress syndrome (ARDS), and to simulate the design and power of the proposed LOTUS trial. Background: A previous study demonstrated improved survival among patients with ARDS receiving tidal volume (Vt) targeted to 6 ml/kg of predicted body weight (PBW). As a result, low–tidal volume ventilation (LTVV) is now recommended for all patients with ARDS, although penetration of this evidence-based practice has been limited, especially early in mechanical ventilation. LTVV may also benefit patients without ARDS. Consequently, there has been increasing call to apply LTVV for all patients with acute respiratory failure upon initiation of mechanical ventilation. The PETAL Network considered performing a pragmatic stepped-wedge, cluster-randomized, controlled, hybrid implementation trial to examine systematic implementation of a default 6 ml/kg PBW LTVV strategy in patients with acute respiratory failure requiring intubation to improve adherence to LTVV and decrease mortality in acute respiratory failure. Trial planning may be better estimated by simulation than routine, simplistic calculations, but such simulations require detailed data of initial parameters. Participants: 2848 patients from 49 hospitals were enrolled. Enrollment varied by hospital, ranging from 4 to 100 patients, the maximum enrollment allowed per site. Design: PETAL-LOTUS FRUIT was a multicenter, prospective, observational cohort study of patients with acute respiratory failure on mechanical ventilation in the PETAL Network hospitals. For all patients, baseline demographic data, the hospital location, indication for intubation (hypoxemic or hypercapnic respiratory failure or both, altered level of consciousness, or surgery), type of intensive care unit (ICU), and Sequential Organ Failure Assessment score in the first 24 hours after intubation were collected. Baseline ventilator data immediately after intubation, arterial blood gas results and oxygen saturation as measured by pulse oximetry, and presence of ARDS was also collected for all patients. ARDS was defined as a ratio of arterial oxygen tension to fraction of inspired oxygen (FiO2) less than or equal to 300 with a chest radiograph within 24 hours of the qualifying ratio of arterial oxygen tension to FiO2 that had bilateral infiltrates unexplained by mass, collapse, or effusion. For the first 50 patients enrolled at each hospital, daily data on ventilator mode, Vt, and presence of ARDS for the first 3 days after intubation was collected. Vt indexed to PBW was calculated from the set Vt for patients on ventilator mode with volume settings. For patients on pressure ventilation modes, Vt was calculated from the ratio of minute ventilation (in ml/min) to the respiratory rate. Enrolled patients were followed until hospital discharge or 28 days for clinical outcomes including mortality, ventilator-free days, and length of stay. To determine the possible improvement in mortality that could be observed with a reduction in Vt from current usual care in the PETAL-LOTUS FRUIT cohort to 6 ml/kg PBW, mortality was estimated as a function of initial Vt. Five models based on data from three distinct patient populations were used. 500 simulations of a stepped-wedge, cluster-randomized clinical trial using the model with greatest predicted benefit for lowering the Vt to 6 ml/kg PBW in PETAL-LOTUS FRUIT sites were performed. Conclusions: Use of initial tidal volumes less than 8 ml/kg predicted body weight was common at hospitals participating in the PETAL Network. After considering the size and budgetary requirement for a cluster-randomized trial of LTVV versus usual care in acute respiratory failure, the PETAL Network deemed the proposed trial infeasible (PMID: 30407869).

  Study phs003791

• ASD WGS DAC

  This data access committee will oversee the request for applications to whole genome sequencing data (WGS) generated at The Centre for Applied Genomics (TCAG), as part of our Autism Genome Project.

  Dac EGAC50000000279

• Japanese population-specific reference panels (BioBank Japan genotype data)

  Develop Japanese population-specific reference panels to improve imputation quality for GWAS

  Study JGAS000738

• V2_Colorectal_panel_test

  Targeted gene screen of cell line tumour samples for testing the new V2 Colorectal gene panel.

  Study EGAS00001001806

• COMPASS Next Generation Sequencing WGS data

  Whole genome sequencing data for Pancreatic Cancer Samples from the COMPASS clinical trial

  Study EGAS50000001091

• WGBS files for PCGP NBL_MYCN_ATRX

  WGBS files for PCGP NBL_MYCN_ATRX paper titled "MYCN Amplification and ATRX Mutations are Incompatible in Neuroblastoma"

  Dataset EGAD00001004559

• McGill EMC Release 4 for cell type "induced pluripotent stem cell"

  McGill EMC Release 4 for cell type "induced pluripotent stem cell"

  Dataset EGAD00001001276

• McGill EMC Release 4 for assay "Bisulfite-seq"

  McGill EMC Release 4 for assay "Bisulfite-seq": Methylation profiling by high-throughput sequencing

  Dataset EGAD00001001289

• McGill EMC Release 4 for assay "RNA-seq"

  McGill EMC Release 4 for assay "RNA-seq": Transcriptome profiling by high-throughput sequencing

  Dataset EGAD00001001290

• McGill EMC Release 4 for assay "mRNA-seq"

  McGill EMC Release 4 for assay "mRNA-seq": Transcriptome profiling by high-throughput sequencing

  Dataset EGAD00001001291

• McGill EMC Release 4 for assay "smRNA-seq"

  McGill EMC Release 4 for assay "smRNA-seq": Transcriptome profiling by high-throughput sequencing

  Dataset EGAD00001001292

• Xenograph files for PCGP SJERG

  Additional Xenograph files for PCGP SJERG

  Dataset EGAD00001002741

• Additional data for 01_HepG2_LiHG_Ct1, H3K122ac

  Additional histone modification data, not yet released as part of IHEC, for cell line 01_HepG2_LiHG_Ct1, H3K122ac.

  Dataset EGAD00001005954

• Deep sequencing for ctDNA determination

  Targeted deep sequencing for the KRAS p.Gly12Asp, p.Gly12Val and p.Ala146Thr mutations in plasma samples of CRC patients.

  Dataset EGAD00001006105

• SNP data for Ovarian cancer PRS (controls)

  SNP data of 28 sites required for the Ovarian cancer PRS (controls)

  Dataset EGAD00001008145

• Genome-wide characterization of Kuwaiti Arab Population

  All the 620 individuals were genotyped using Illumina HumanOmniExpress arrays for 730,525 SNPs.

  Study EGAS00001005034

• NHLBI TOPMed - NHGRI CCDG: The Johns Hopkins University School of Medicine Atrial Fibrillation Genetics Study

  Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is the primary cause of many hospital admissions, and is associated with significant secondary morbidity by increasing the risk of stroke, heart failure, and all-cause mortality. The incidence of AF is on the rise, and it is projected that by the year 2050 more than 10 million patients will be affected by AF in the United States alone. Anti-arrhythmic medications have limited success in maintaining sinus rhythm, are associated with side effects, and appear ineffective at reducing mortality compared to a strategy of rate control and anticoagulation. Given the significant morbidity associated with this common arrhythmia, surgical and catheter ablation techniques have been developed to treat AF. However, despite the incorporation of various strategies for ablation, long-term recurrence rates of AF remain higher than 25 percent after ablation. Current techniques for catheter ablation of AF include pulmonary vein isolation and complex fractionated atrial electrogram (CFAE) ablation. However, the contribution of each strategy to long-term procedural success and the relative importance of each strategy for different patients remain unknown. Recent advances in cardiac imaging have allowed detailed analysis of left atrial myocardial anatomy. Parallel advances in molecular genetics have identified several candidate genes involved in familial and non-familial AF. However, the pathophysiology of AF generation and maintenance, and the potential contribution of such genetic or anatomic substrates for patient selection, and for target identification during catheter ablation have not yet been examined. Advances in molecular genetics and imaging, coupled with techniques for endocardial and epicardial mapping in the electrophysiology laboratory present an opportunity to significantly improve our understanding of (1) The relation of paroxysmal versus persistent AF with (a) structural left atrial changes (left/right atrial scar, wall thinning, pulmonary vein anomalies, and coronary sinus dilation) and with (b) candidate genetic variants. (2) The relation of candidate genetic variants with (a) structural left atrial changes and with (b) electrophysiologic properties (atrial effective refractory period (AERP) inhomogeneity, voltage abnormalities, trigger burden and location, C FAE extent and location), (3) The relation of structural left atrial changes with (a) CFAE location as targets for catheter ablation and with (b) reversible conduction block/myocardial injury after pulmonary vein isolation, and (4) Individualized endocardial targets for AF ablation based on candidate genes and anatomic substrates. The proposed study will improve our understanding of the underlying pathophysiology of AF, and may improve current techniques for treatment of this important arrhythmia.

  Study phs001598

• Assessment of RNA-Seq Sample Preparation Methodology

  The goal of this study was two-fold, to determine if common purification techniques have any effect on downstream differential expression analysis and to evaluate combinations of alignment and differential expression software for reliability. To this end, blood was collected from three individuals and pooled during and after extraction. After pooling and mixing was completed, samples were divided into three aliquots for testing. The first aliquot was a control and not purified or concentrated. It was diluted to produce samples of varying concentrations for testing. The second aliquot was diluted to 20 ng/μL and used to test six different variations on the AMPure XP bead purification procedure. The last aliquot was also diluted to varying concentrations of 60, 30, and 9.6 ng/μL and purified using MinElute columns. Samples were submitted for total RNA-Seq library preparation and sequencing. Library preparation was performed using the TruSeq Stranded Total RNA with Ribo-Zero Globin kit (20020612, Illumina Inc.), and 2x150 bp PE sequencing was done on an Illumina NovaSeq 6000 with the S4 reagent kit. Comparisons were made between methods (AMPure vs. unpurified, AMPure vs. MinElute, MinElute vs. unpurified) to assess the effects of purification method on downstream differential expression. Comparisons were also made within methods using the varying concentrations tested for unpurified samples and for MinElute purified samples to assess the effects of concentration on differential expression. Variations of the AMPure procedure were also compared to assess the effectiveness of the variations tested in comparison to the unmodified procedure. A subset of samples was selected for use with alignment and differential expression package comparison. Unpurified high concentration samples eluted in RNAse-free water were compared to unpurified high concentration samples eluted in BR5, a buffer from the PAXgene blood miRNA kit, with the expectation that there should be no or very few differentially expressed genes. Unpurified high concentration samples eluted in RNAse-free water were also compared to unpurified low concentration samples also eluted in RNAse-free water, with possibly a small number of differentially expressed genes anticipated. A third dataset of simulated RNA-seq data was created with a known rate of differential expression. These files were aligned using Bowtie2, HISAT2, kallisto, RSEM, Rsubread, Salmon, and STAR. Results were then analyzed for differential expression using ALDEx2, baySeq, DEGseq, DESeq2, edgeR, limma, NOISeq, PoissonSeq, and SAMseq. Differential expression results of all three comparisons were evaluated to determine which combinations provided the most reliable results for both real and simulated data.

  Study phs003001

• Genetic Analysis of Normal Human Facial Variation

  The purpose of this project is to identify genes associated with normal human quantitative facial variation. The motivation for this project stems from the fact that very little is known about how variation in specific genes relates to the diversity of facial forms commonly observed in humans. Viable candidates for these morphogenes originate from a number of sources: tissue expression studies, animal models with targeted or spontaneous mutations, and genetic syndromes with craniofacial manifestations. Importantly, understanding the genetic basis for normal facial variation also has important implications for health-related research. For example, this work has the potential to shed light on the factors influencing liability to common craniofacial anomalies such as orofacial clefts. There is now ample evidence that certain facial features (e.g., increased midfacial retrusion) characterize individuals genetically at-risk for orofacial clefts (e.g., biological relatives of affected cases). While these predisposing facial features are statistically over-represented in at-risk groups, they are also common in the general population. Since many of the current candidate genes for clefting are thought to play a critical role in facial morphogenesis, variation in these genes may also underlie normal variation in these facial features. These candidate genes, however, probably represent only a small fraction of the total number of loci influencing normal human facial variation. Phenotypes for this project were obtained from over 3000 healthy Caucasian subjects recruited through three separate studies. The majority of the subjects were recruited as part of the 3D Facial Norms Project, which is described in extensive detail here: (https://www.facebase.org/facial_norms/notes). The provided dbGaP phenotypes include a series of anthropometric craniofacial measurements (linear distances) primarily derived from 3D photographic facial surface scans (see previous hyperlink). The specific genotyping requested is described elsewhere in this document. Our analysis team is pursuing a variety of different analytic approaches to derive genetically informative phenotypes, including various shape-based morphometric methods. For those interested in pursuing more advanced phenotypic approaches, the original 3D surface scans and additional phenotypic traits are available to researchers through the FaceBase Consortium. This dataset has the potential to facilitate the discovery of new genetic loci with an important role in both normal and abnormal facial development. It may also serve as a dataset to test hypotheses regarding specific SNP associations (e.g. as a replication dataset) or as part of a larger meta-analysis.

  Study phs000949

• Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION-BioLINCC)

  Accessing Data Please refer to “Authorized Access” below regarding accessing data through the BioData Catalyst ecosystem. The data from this accession is not available for download through dbGaP.ObjectivesThe HF-ACTION study examined whether exercise training reduces a composite endpoint of all-cause mortality or all-cause hospitalization for patients with left ventricular systolic dysfunction and heart failure symptoms. Background Heart failure (HF) is a major and growing cardiovascular syndrome that is the end result of many cardiovascular disorders. Although evidence-based drug and device therapies decrease mortality, hospitalizations, and HF symptoms and improve quality of life, many patients treated with these regimens often remain burdened by dyspnea and fatigue, diminished exercise tolerance, reduced quality of life, recurrent hospitalizations, and early mortality. Whereas rest was traditionally recommended for HF patients, there has been evidence that physical deconditioning may play a key role in the progression of symptoms and poor outcomes. Previous studies have shown positive effects of exercise training on exercise capacity, quality of life, and biomarkers and suggest that exercise training might improve survival and decrease HF hospitalizations. Nonetheless, there remains a safety concern regarding exercise training in HF and a large scale, multicenter, controlled clinical trial was needed to provide definitive clinical outcome data. Participants A total of 2,331 participants were randomized. 2,130 consented to share data with non-commercial entities, and 1,753 consented to share for commercial purposes. Design All participants underwent baseline cardiopulmonary exercise testing. Test results were reviewed by investigators to identify significant arrhythmias or ischemia that would prevent safe exercise training, to determine appropriate levels of exercise training, and to establish training heart rate ranges. Demographics, socioeconomic status, past medical history, current medications, physical exam, and the most recent laboratory tests were obtained prior to randomization. All participants received detailed self-management educational materials which included information on medications, fluid management, symptom exacerbation, sodium intake, and physical activity. Participants randomized to the exercise training arm first participated in a structured, group-based, supervised exercise program, with a goal of 3 sessions per week for a total of 36 sessions in 3 months. The primary exercises were walking, treadmill, or stationary cycling. Exercise was initiated at 15 to 30 minutes per session at a heart rate corresponding to 60% of heart rate reserve, and was increased after 6 sessions to 30 to 35 minutes duration and 70% of heart rate reserve. Participants began home-based exercise after completing 18 supervised sessions and were to fully transition to home exercise after 36 supervised sessions. The target training regimen for home exercise was 5 times per week for 40 minutes at a heart rate of 60% to 70% of heart rate reserve. Participants randomized to the usual care group were not provided with a formal exercise prescription. To provide comparable levels of attention from study personnel, all participants were called every 2 weeks for the first 9 months, monthly until 24 months of follow-up, and quarterly thereafter. Participants returned for clinic visits every 3 months for the first 2 years of participation and yearly thereafter for up to 4 years. Follow-up assessments included cardiopulmonary exercise testing, a 6-minute walk test, and a physical activity questionnaire. The primary end point was a composite of all-cause mortality or all-cause hospitalization. Secondary end points included all-cause mortality, the composite of cardiovascular mortality or cardiovascular hospitalization, and the composite of cardiovascular mortality or HF hospitalization. Conclusions After adjustment for highly prognostic predictors of the primary end point, exercise training was associated with modestly significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization.

  Study phs003599

• Roifman DAC

  This Data Access Committee will oversee all requests for data submitted by Dr. Chaim Roifman at the Hospital for Sick Children in Toronto, Canada. Requests should be directed by email to chaim.roifman@sickkids.ca.

  Dac EGAC50000000396

• DAC for Studies of "Genetics and Genomics of Cardiovascular Diseases" Group at MDC Berlin, Germany

  DAC for Studies of "Genetics and Genomics of Cardiovascular Diseases" Group at MDC Berlin This is an umbrella DAC.

  Dac EGAC50000000481

• Single cell whole genome sequencing of 5 ovarian cancer specimens

  Single cell whole genome sequencing BAM files for five ovarian cancer specimens.

  Study EGAS50000001458

• GBM cancer stem cell lines -RNA-seq and WGS data

  Glioblastoma stem cell lines have been profiled for RNA-seq and WGS

  Study EGAS00001003700

• WTCCC2 project Glaucoma (GL) samples

  A WTCCC2 genome-wide association study for glaucoma (GL) in Australian individuals of European descent.

  Study EGAS00001000624

• Colorectal cancer functional annotation - ChIP

  ChIP-seq data for multiple colorectal cancer cell lines (H3K4me1, H3K4me3, H3K27ac, H3K27me3, H3K36me3, CTCF)

  Study EGAS50000000207

• DEEP IHEC release 2017

  Raw data files for DEEP's IHEC/EpiRR submission of 2017. metadata available at: http://deep.dkfz.de/#/experiments

  Study EGAS00001002655

• CRISPR_screen_M14__NCI_H3122

  Genome wide CRISPR screen was performed to find resistance to targeted drugs for melanoma and lung

  Study EGAS00001001060

• EM-seq converted WGS for CSF-derived cfDNA from pediatric brain tumor patients

  EM-seq converted WGS for CSF-derived cfDNA from pediatric brain tumor patients

  Dataset EGAD50000001975

• OLD DATA FILES FOR SJMB - Superseded by EGAD00001001864

  OLD DATA FILES FOR SJMB - Superseded by EGAD00001001864

  Dataset EGAD00001000269

• DATA FILES FOR SJACT (WGS)

  DATA FILES FOR SJACT

  Dataset EGAD00001000160

• DATA FILES FOR SJEPD

  DATA FILES FOR SJEPD

  Dataset EGAD00001000162

• UKBEC 1st release of Exome data for 65 individuals

  UKBEC 1st release of Exome data for 65 neuropathologically confirmed control individuals of European descent.

  Dataset EGAD00001003100

• DATA FILES FOR GRUBER SJAMLM7 RNASEQ

  DATA FILES FOR GRUBER SJAMLM7 RNASEQ

  Dataset EGAD00001003135

• McGill EMC Release 4 in tissue "venous blood" for cell type "eosinophil"

  McGill EMC Release 4 in tissue "venous blood" for cell type "eosinophil"

  Dataset EGAD00001001281

• McGill EMC Release 4 in tissue "venous blood" for cell type "Monocyte"

  McGill EMC Release 4 in tissue "venous blood" for cell type "Monocyte"

  Dataset EGAD00001001282

• Maternal Plasma RNA Sequencing for Genomewide Transcriptomic Profiling and Identification of Pregnancy-Associated Transcripts

  Maternal Plasma RNA Sequencing for Genomewide Transcriptomic Profiling and Identification of Pregnancy-Associated Transcripts

  Dataset EGAD00001001609

• Somatic SNVs and Indels for INSPIRE Tumor WES

  Somatic SNVs and Indels for INSPIRE Tumor WES called using Mutect, Mutect2, Varscan2, Vardict, and Strelka2

  Dataset EGAD00001006569

• RNASeq files for Mullighan ECOG2993 data

  RNASeq files for paper titled "Molecular classification improves risk assessment in adult B-lineage ALL: Patients on the international UKALLXII-ECOG2993 trial."

  Dataset EGAD00001006380

• Remaining WGS files for Klco RPAML data

  Remaining WGS files for study titled "Genomics of pediatric myeloid neoplasms"

  Dataset EGAD00001008446

• WGBS for APL

  Whole genome bisulfite sequencing (WGBS) for APL

  Dataset EGAD00001008136