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• Summary statistics from genome-wide association study in glioma of 12,488 cases and 18,169 controls.

  Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,488 cases and 18,169 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10-9, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10-10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10-11, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10-10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10-9, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10-10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10-10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10-9, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10-10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10-11, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10-9, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.

  Study EGAS00001003372

• Acute Respiratory Distress Network (ARDSNet) Studies 10 and 12 Statins for Acutely Injured Lungs from Sepsis (SAILS) (ARDSNet-SAILS-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-SAILS include Plasma, DNA, and Urine. Please note that use of biospecimens in genetic research is subject to a tiered consent. Objectives The SAILS trial was intended to assess the efficacy and safety of oral rosuvastatin in participants with sepsis-induced Acute Lung Injury (ALI) and test the hypothesis that rosuvastatin therapy would improve the clinical outcomes of critically ill participants with sepsis-associated acute respiratory distress syndrome (ARDS). Background In ARDS, inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in participants with sepsis. Participants There were 745 participants. Design Participants were randomly assigned in permuted blocks to receive either enteral rosuvastatin or placebo. A 40 mg loading dose of the study drug was administered within four hours after randomization. Subsequently, maintenance doses of 20 mg were administered daily until the third day after discharge from the intensive care unit, study day 28, hospital discharge, or death, whichever came first. The primary outcome measure was mortality before hospital discharge home or until study day 60 if the participant was still in a health care facility. Secondary outcome measures included the number of ventilator-free days to day 28, organ-failure-free days to day 14, and ICU-free days to day 28. Conclusions The study was stopped because of futility after 745 of an estimated 1000 participants had been enrolled. There was no significant difference between study groups in 60 day in-hospital mortality or in mean ventilator-free days. The rosuvastatin group had fewer days free of hepatic or renal failure. Thus, rosuvastatin therapy did not improve clinical outcomes in participants with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.

  Study phs003736

• Single Cell and Spatial Transcriptomic Profiling of Haemophilus ducreyi Infection

  We investigated the immune response in end-point pustules formed by Haemophilus ducreyi in volunteers using an experimental infection model. Six volunteers were infected in the skin of the upper arm at three sites with 41-85 CFU of H. ducreyi loaded on an allergy testing device; a sham-inoculated (e.g., wound) site was also performed. Five volunteers (4 men and 1 woman; 2 Asians and 3 Whites; aged 27-46 years) formed pustules 6-8 days post infection; 1 volunteer spontaneously resolved all sites. If a volunteer formed pustules, biopsies were performed to collect their pustule and wound sites. Biopsy pairs for all 5 pustule formers were subjected to single cell (sc) RNA-seq. Sequencing libraries were prepared using the 10X Genomics Single-cell 3' RNA-seq kit. Spatial transcriptomics was performed on biopsy pairs from 4 of the 5 pustule formers. Ten micron sections were placed on 10X Genomics Visium slides for fresh-frozen tissue, and libraries were prepared with the 10X Genomics Visium spatial 3' gene expression kit. All samples were sequenced on an Illumina NovaSeq 6000. Count tables were produced with CellRanger and SpaceRanger, respectively, and Seurat was used to analyze the data. We identified 13 major cell types by scRNA-seq; the proportion of some immune cell subsets was increased in pustules compared to wound sites. We also localized the major cell types within the tissue by using the scRNA-seq data to deconvolve the spatial transcriptomic data. The FASTQ files and count tables from CellRanger and SpaceRanger are provided.

  Study phs003754

• Transcriptional Profiling of PD-1+ and PD-1- Teff and Treg Cells in Glioblastoma and Health

  PD-1 is an important immune checkpoint inhibitor that shows great promise in the clinic, particularly for melanoma and lung cancers. Since PD-1 is also expressed on infiltrating CD4+ Treg and Teffector cells in glioblastoma, we sought to better understand the role of PD-1 on these infiltrating CD4+ Treg and Teffector cells. To this end, we performed functional and transcriptional profiling using CD4+ Treg and Teffector cells isolated from healthy donors and glioblastoma patients (from both tumors and blood).

  Study phs001079

• Integrated multi-omics analysis of pediatric hepatoblastoma

  Hepatoblastoma (HBL) is the most common malignant liver tumor in childhood and is clinically heterogeneous. In spite of its heterogeneity, the molecular basis responsible for the difference between low-risk and high-risk HBL has not been fully clarified. To address this issue, we carried out multi-omics analysis on 59 HBL samples to generate comprehensive profiles of gene mutation, copy-number alteration, DNA methylation and gene expression. By integrating these data, we aimed to unravel the heterogeneity of HBL and identify genetic determinants and therapy targets of high-risk HBL.

  Study JGAS000188

• Long-Term Oxygen Treatment Trial (LOTT-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: To evaluate the efficacy of long-term treatment with supplemental oxygen in people with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation. Background: COPD is the fourth leading cause of death in the United States, with more than twelve million people currently diagnosed with the disease. In 2011, Medicare reimbursements for oxygen-related costs for people with COPD exceeded two billion dollars. The quality of life of a person with COPD decreases as the disease progresses, making treating and managing COPD in the moderate stages important. The benefits of oxygen supplementation were studied in the 1970s, but these benefits were specific to people with COPD who have severe resting hypoxemia. The LOTT trial was designed to address the effectiveness of supplemental oxygen therapy in treating people with COPD who have moderately low blood oxygen levels at rest or who have normal blood oxygen levels at rest, but have low or very low blood oxygen levels during exercise. Participants: There were a total of 1759 people screened for eligibility for the LOTT trial. Of the 1759 screened, 738 people with COPD were selected for randomization with 368 randomly assigned to the supplemental-oxygen group and 370 to the no-supplemental-oxygen group. Of the 738 people with COPD who underwent randomization, 133 (18%) had resting desaturation only, 319 (43%) had exercise-induced desaturation only, and 286 (39%) had both types of desaturation. Furthermore, in the supplemental-oxygen group, 220 people were prescribed 24-hour oxygen and 148 were prescribed oxygen during exercise and sleep only. Design: The LOTT trial was originally designed to test whether the use of supplemental oxygen would result in a longer time to death for people with COPD and moderate resting desaturation. After seven months, the trial design was judged to be infeasible; therefore, the trial was redesigned to include people with exercise-induced desaturation with a primary composite outcome of death or first hospitalization for any cause, whichever occurs first. Other outcomes measured included: death, health care utilization, COPD exacerbation, quality of life measurements, anxiety, depression, and measures of functional status. Potential participants were screened using questionnaires, a breathing test, a brief physical exam, a blood draw, and measurements of resting and walking blood oxygen levels. Based on those results, eligible participants returned for a second screening visit for further evaluations. At the end of the second visit, eligible participants were assigned randomly to supplemental oxygen therapy or no oxygen therapy. Participants assigned to supplemental oxygen therapy received stationary and/or portable oxygen systems. Participants were required to return for a one hour visit to determine how much oxygen to use while walking and to learn how to use the equipment. Participants who had low blood oxygen levels during rest were instructed to use supplemental oxygen 24 hours per day. Participants with normal resting blood oxygen levels, but low or very low blood oxygen levels during exercise were instructed to use it during physical activity and sleep. Throughout the treatment period, participants were asked to keep records of the number of oxygen tanks emptied or pounds of oxygen delivered, meter readings, and changes in equipment. Study officials contacted participants weekly for the first month, monthly for the next five months, and then every two months until the Year 1 study visit. Participants assigned to receive no oxygen treatment were contacted one week after assignment for a check-up. All participants returned for study visits once a year for up to seven years. At each of these visits, participants completed some of the same tests and questionnaires from the screening visit. Participants underwent a blood draw during the one year study visit. Participants in both treatment groups received two phone calls each year to check on status and use of oxygen. In addition, participants in both groups were asked to complete a quality of life questionnaire by mail at four months and sixteen months. Medicare claims were collected for the duration of each participant's enrollment in the study. Conclusions: In participants with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. Long-Term Oxygen Treatment Trial Research Group, Albert RK, Au DH, Blackford AL, Casaburi R, Cooper JA Jr, Criner GJ, Diaz P, Fuhlbrigge AL, Gay SE, Kanner RE, MacIntyre N, Martinez FJ, Panos RJ, Piantadosi S, Sciurba F, Shade D, Stibolt T, Stoller JK, Wise R, Yusen RD, Tonascia J, Sternberg AL, Bailey W. A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-1627.

  Study phs003933

• RBWES

  Retinoblastoma is a rare childhood cancer of the retina. We studied retinoblastoma by Whole-Exome-Sequencing.

  Dataset EGAD00001007591

• Amplicon sequencing data from organoids of colorectal cancer patients.

  The dataset includes 13 bam files. Each bam file is a different colorectal cancer patient organoid.

  Dataset EGAD00001004313

• FRIGE IHG Data Access Committee reviews the aim and methodology of the proposed study for which access to anonymised data is requested.

  Dac EGAC00001003629

• Targeted RNA-Seq

  This dataset contains targeted RNA-Seq generated with the Illumina RNA Pan-Cancer panel. It comprises 2200 cancers from children and adults. The cancers represent a wide range of CNS, solid and haematopoietic tumours. Samples are from pathology specimens including FFPE, fresh frozen, bone marrow aspirate and peripheral blood. Samples were tested in a clinical diagnostic lab to identify relevant SNVs, indels and gene fusions.

  Dataset EGAD50000000980

• Transcriptomic dataset from a phase II study of pembrolizumab and epigenetic modification with azacitidine in platinum-resistant epithelial ovarian cancer

  This dataset includes sequence files from bulk RNA sequencing of tissue biospecimens from a phase II study investigating epigenetic priming followed by immune checkpoint blockade in platinum-resistant epithelial ovarian cancer (NCT02900560). There are 48 bulk RNA sequencing files from 24 specimens included in this dataset.

  Dataset EGAD50000001664

• Innate immune cell subsets are enriched in synovial fluid of ACPA-negative rheumatoid arthritis and characterised by distinct type I IFN gene signatures

  This study provides a detailed comparison of the myeloid cell landscape in the SF of patients with ACPA+ and ACPA− RA, highlighting the unique involvement of type I IFN responses in ACPA− RA.

  Study EGAS50000001260

• single-cell RNA-seq profiling of 2 patient derived colorectal cancer organoids after treatment with a combination of different anticancer drugs

  This dataset consists of single-cell RNA-seq profiling of colorectal cancer organoids derived from two patients. The organoids were profiled both after 4 weeks of treatment and after a drug holiday of two weeks. There are 49 RNA sequence files generated using single cell RNA sequencing technology from 10X genomics.

  Dataset EGAD50000001495

• Exome sequencing from a child with neurofibromatosis and relapsed refractory acute lymphoblastic leukaemia

  Dataset contains 5 exome BAM files from a child with neurofibromatosis and relapsed refractory acute lymphoblastic leukaemia. The samples are CD19 positive and CD19 negative bone marrow mononuclear cells at both diagnosis and relapse as well as mesenchymal stem cells as the germline control. Libraries were prepared using the SureSelect Clinical Research Exome v2 kit (Agilent Technologies, Santa Clara, CA, USA) and run on the Illumina NextSeq 500 platform.

  Dataset EGAD00001008702

• Single-cell Multi-omics Sequencing of Human Early Embryos

  The whole blood of six female volunteers and sperm from one male volunteer were used to extract genomic DNA using a DNeasy Blood & Tissue Kit (QIAGEN). 500 ng gDNA was fragmented into 300 bp by Covaris. Then, the libraries were constructed using a KAPA Hyper Prep Kit (Kapa Biosystems). In total we have 7 samples and the files we uploaded are pair-end fastq files.

  Dataset EGAD00001004108

• Cellular Analysis of Resistance and Evolution in IDH-mutant glioma

  We profiled a total of 75 IDH-mutant gliomas to study tumor evolution in this tumor type, among which 51 samples are presented here. These data reflect a combination of whole genome sequencing, whole exome sequencing, 10x single nucleus RNA sequencing, and 10x simultaneous single nucleus RNA and ATAC sequencing.

  Dataset EGAD50000002485

• Raw ONT R9 data: Rapid brain tumor classification from sparse epigenomic data

  This dataset contains 75 Nanopore sequencing experiments using a MinION sequencer and R9 flow cells from 51 patient biopsies. Gzipped tar files containing all fast5 files per sample are provided.

  Dataset EGAD50000000832

• Single-cell paired sequences from intraepithalial CD8+ αβ T-cells from celiac disease patients and controls

  Paired T-cell receptor sequences sequenced from single cells, from intraepithalial CD8+ αβ T-cells. Sequences are from from untreated and treated (on a gluten-free diet) celiac disease patients and controls.

  Dataset EGAD00001006900

• Xenograft cfDNA dataset

  The dataset contains 16 xenograft plasma cfDNA samples from mice grafted with a human colorectal cell line. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001011128

• Methylome profiling of Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) and a patient derived cell-line model

  Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using the twist human methylome panel.

  Dataset EGAD50000000040

• ENU-HT-29 BRAF Triple Therapy Clones

  KRAS mutant CRC is currently in clinical trial with a combination of a MEK and Akt inhibitor. These patients will likely develop resistance to this combination. We aim to identify the mechanisms of resistance via ENU mutagenesis, with a view to identifying additional therapeutics which have the ability to overcome this resistance.

  Dataset EGAD00001002066

• Transcriptional consequences of SETBP1 variants in developmental disorders and malignancies

  The SETBP1 gene encodes a DNA-binding nuclear protein that regulates gene expression across multiple tissues. Precise control of SETBP1 dosage is essential for normal cellular function, as both loss- and gain-of-function variants of SETBP1 can lead to severe phenotypic consequences. De novo germline gain-of-function point mutations that prolong SETBP1 half-life result in Schinzel-Giedion syndrome (SGS), an ultra-rare and severe congenital disorder associated with extensive developmental abnormalities and health complications. These SGS-associated variants cluster within a hotspot in the SKI-homology domain of SETBP1, overlapping with somatic mutations recurrently observed in myeloid leukaemia with poor prognosis. Thus far, the precise mechanisms by which these SETBP1 mutations drive disease remain largely unclear. Here, through single-cell and single-nucleus mRNA sequencing of a rare collection of primary patient samples with SGS and myeloid leukaemia, we examined the transcriptional consequences of SETBP1 gain-of-function variants in haematopoietic cells, comparing their impacts when acquired in the germline and somatically in malignancies.

  Dataset EGAD00001015482

• Whole-exome sequencing and microRNA profiling predicted relapse risk of stage I lung adenocarcinomas for the study and all the datasets.

  This dataset contains PAIR files and processed somatic copy number alteration value for array CGH of stage I lung adenocarcinomas from Asian patients. In total, there are 111 patients and 222 samples, including 111 tumor samples and 111 adjacent normal samples.

  Dataset EGAD00010001902

• CRITICS trial Whole Exome Sequencing (WES)

  Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Molecular characterisation of N=36 resectable gastric adenocarcinomas from CRITICS trial, describing mutations obtained by matched (Tumor-Normal) whole exome sequencing (WES). Samples are annotated for TCGA’s molecular classification (MSI, GS and CIN).

  Dataset EGAD50000001145

• EGA dataset for High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube

  The dataset for High Grade Serous Ovarian Carcinomas Originate in the Fallopian Tube includes 46 bam files from next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include multiple lesions from nine patients, five with high grade serous ovarian carcinoma and four who are BRCA-carriers.

  Dataset EGAD00001003792