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• Genome-Wide Association Study of HIV-1 Host Genetics Among Injection Drug Users

  The overarching goal of this project is to identify and characterize genetic determinants of HIV 1 susceptibility and resistance in samples of African American (AA) and European American (EA) injection drug users (IDUs) by conducting (1) a case/control genome-wide association (GWA) study of HIV 1 infection (positive/negative); (2) a case-only GWA study of viral load among HIV+ IDUs. The study uses existing samples and data from Urban Health Study (UHS) (PI: Alex Kral), which was the longest-running study of street-recruited IDUs in North America, from 1986-2005. UHS was a serial, cross-sectional sero-epidemiological study. Data were collected every 6 months in communities with a high prevalence of injection drug use in the San Francisco Bay Area. It used targeted sampling in neighborhoods at easily accessible community field sites, such as churches, single room occupancy hotels, and community centers. Eligibility criteria for initial entry to the study were (1) injection drug use in past 30 days; (2) ability to provide informed consent; and (3) age 18 or older. The UHS cohort includes over 9,000 African American and European American IDUs whose serum samples have been stored and data are available on HIV antibody status, HIV risk behaviors, drug abuse and demographics. The current study includes 985 HIV+ cases and 5,222 HIV- controls. Approximately six HIV- controls per case were frequency matched on: (1) self-reported ancestry; (2) sex; (3) age; (4) year of ascertainment; and (5) HIV risk class. This GWAS (DA026141) was funded by the National Institute on Drug Abuse (NIDA; PI: Eric O. Johnson). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR), was provided by NIDA and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C).

  Study phs000454

• Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure with Preserved Ejection Fraction (INDIE-HFpEF): Heart Failure Network (HFN INDIE-Imaging)

  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. Objective: To determine the effect of inhaled, nebulized inorganic nitrite on exercise capacity in patients with heart failure with preserved ejection fraction.Background: Approximately half of patients with heart failure have a preserved ejection fraction (HFpEF). However, there are no proven effective medical treatments for this syndrome. Evidence suggests that impairments in nitric oxide availability have a potentially important role in the pathophysiology of HFpEF.Unlike organic nitrates, inorganic nitrite is converted to nitric oxide in the presence of hypoxia and acidosis, conditions that develop during exercise. Because the cardiac, vascular, and skeletal muscle abnormalities that limit physical capacity and contribute to symptoms in patients with HFpEF characteristically develop during exercise, inorganic nitrite may provide the best way to target nitric oxide delivery precisely at the time of greatest need. The HFN-INDIE trial was initiated to test the hypothesis that compared to placebo, longer-term use of inhaled, nebulized inorganic nitrite would enhance peak exercise capacity in patients with HFpEF. Participants: A total of 105 participants were randomized. 53 were randomized to receive nitrite first and 52 were randomized to receive placebo first.Design: HFN-INDIE was a multicenter, randomized, double-blind, placebo-controlled, crossover study. After enrollment, patients underwent baseline studies to determine eligibility. All patients were required to display objective exercise limitation, evidenced by reduced peak oxygen consumption (V̇o2) on cardiopulmonary exercise testing of less than 75% predicted, with a respiratory exchange ratio indicative of maximal effort (≥1.0). Following qualifying exercise testing, eligible participants received an open-label, single-dose run-in of inhaled, nebulized sodium nitrite (80 mg) to assess tolerability, symptoms, and orthostatic vital signs. Patients developing hypotension (systolic blood pressure The prespecified primary end point was peak V̇o2, measured as the highest 30-second average during upright cycle ergometry, during the 4-week period in which patients were receiving inorganic nitrite as compared with placebo. Accelerometry, health-related quality-of-life scores on the self-administered Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores indicating better quality of life), echocardiographic indicators of cardiac filling pressures measured at trough drug levels (E/e′ ratio, estimated pulmonary artery systolic pressure, and left atrial volume index; lower scores indicate better health for all), ventilatory efficiency (VE/V̇co2, lower indicating better health), exercise time (higher indicating better health), and NT-proBNP levels (lower indicating better health) were also collected.Data Availability: Data available from this study includes transthoracic echocardiogram images from multiple timepoints. There are 199 echocardiographic exams available, totaling over 13,100 individual echocardiogram images. Conclusions: Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity.Reference: Borlaug et al., 2018, PMID: 30398602.

  Study phs003804

• RNA-seq samples

  Raw FASTQ files obtained by RNA sequencing of tumor samples from patients (age 12-29) with newly diagnosed, recurrent intermediate or high-grade sarcoma.

  Dataset EGAD00001008393

• RNA-Seq data for manuscript titled: A sporadic Alzheimers blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies

  RNA-Seq data for manuscript titled: A sporadic Alzheimers blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies

  Dataset EGAD00001008670

• DNA methylation database for gynecological cancer detection, classification and assay development

  MeD-seq data (fastq files) from gynecological cancers and associated healthy tissues. In total 292 fastq files generated by MeD-seq are deposited consisting of: healthy tissues (vulva n=11, cervix n=15, endometrium n=13, fallopian tube n=18 and ovary n=13), precursor lesions of cancer (vulva n=23 and cervix n=46) and cancer (vulva n=21, cervix n=45, endometrium n=26, fallopian tube n=8 and ovary n=33)

  Dataset EGAD50000000611

• Introducing Federated EGA Affiliates: a newly defined tier in the Federated EGA Network

  We're happy to announce that we are now accepting Affiliates in the Federated EGA Network! Federated EGA is a global network of repositories enabling secure discovery and access to sensitive human data. Currently, Federated EGA consists of Central EGA (CEGA), which serves the global community, and nine national Nodes that serve respective jurisdictions. Did you know that the Federated EGA (FEGA) has always envisioned a third tier within the network? This brings us to FEGA Affiliates, recently defined in the newly approved "Federated EGA Structure and Organisation" document. This new tier broadens the range of institutions or organisations that can become part of FEGA. Thus begins a new era for the network. What is a FEGA Affiliate? A FEGA Affiliate archives and serves controlled-access data within its own governance scope, while still participating in federated discovery through the EGA catalogue. Affiliates can be individual organisations or institutions, healthcare genomics initiatives, consortia of institutions, as well as project-specific consortia (national or international). In practical terms, a FEGA Affiliate: Hosts and safeguards the data it archives. Submits non-personal metadata to CEGA so studies are discoverable and can receive EGA accessions. Manages permissions and data access workflows for its datasets. Provides data access and/or distribution, along with support, to authorised users. Key takeaways about FEGA Affiliates FEGA is now organised into three tiers: CEGA, FEGA Nodes, and FEGA Affiliates. Affiliates archive data from their own organisation and/or selected partner institutions (for example, an international consortium). Affiliates make studies discoverable through the EGA catalogue by submitting non-personal metadata for accessioning. Access decisions and conditions are managed locally by the Affiliate (e.g. distribution or access in a trusted research environment). Are you considering whether your institution or project might be a good fit as a FEGA Affiliate? Would you like to learn more about this tier? We have published a blog post that addresses potential common questions, providing answers on this topic. You can read it here.

  Blog fega-affiliates

• Germline RUNX1 Variation and Predisposition to Childhood Acute Lymphoblastic

  Somatic mutations of RUNX1, which encodes the myeloid and lymphoid transcriptional factor RUNX1, are common in both B- and T- acute lymphoid leukemia (ALL) and are associated with poor prognosis of T-ALL. However, there has been no comprehensive investigation of the pattern or prevalence of RUNX1 germline mutation in both B- and T-ALL. Here we report germline RUNX1 variants in 1.23% of B-ALL and 2.11% of T-ALL, identifying 31 unique variants in 62 B-ALL and 18 unique variants in 26 T-ALL children. The majority of frameshift and nonsense variants affected RUNX1 function in transcriptional regulation, hematopoiesis, and cellular proliferation. We identified JAK3 as the most frequent somatic mutation in T-ALL with RUNX1 variants. These results not only identify RUNX1 as a leukemia predisposition gene but also further underline the importance of germline genetic variants to the development of ALL

  Study EGAS00001005403

• Whole Genome Sequencing of HCC

  The present series corresponds to 24 whole genome sequencing (12 Tumoral/Non-tumoral pairs). Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before.

  Dataset EGAD00001003994

• Advancing fast in the analysis of circulating tumour DNA

  In cancer patients, solid tumours also release DNA fragments into the blood, and they are called Circulating Tumours DNA (ctDNA). Nowadays, the standard procedure for cancer monitoring is analysis of surgically obtained biopsies. They generate a big amount of material, but the operation is highly invasive and provide medical doctors with a single-time snapshot of the tumours, which are often highly changeable. Analysis of ctDNA, on the other hand, can provide continuous information regarding the tumour itself without the need of invasive procedures. This is why interest in this method is growing, and with it, the need for its technological optimization. Guanhua Zhu and colleagues, at the Genome Institute of Singapore, developed a methodology to quantify ctDNA burden, which means to estimate the amount of tumours derived circulating DNA among all cell-free DNA in the blood of individuals. Their work, published in Nature Communications in april 2021 and summarized in a sketch below, uses state-of-the art methods to analyse cfDNA degradation patterns at promoters and exon regions, to discern it from the DNA coming from the tumours. The bright point of their approach is that simultaneously enable for profiling of actionable cancer mutations and quantitative estimation of ctDNA burden. Their sequencing data of ctDNA has been deposited in the EGA under the accession number EGAS00001004657. This study sums up to a total of 37 of cfDNA and 36 about ctDNA present up to date in the EGA archive. The existence of cfDNA was firstly described back in 2002, while the use of ctDNA analysis in the oncological field exploded only after 2016. The approach is rapidly evolving, moving in parallel with the ever-improving sequencing technologies. Especially, the possibility to obtain high quality sequences from minimal amount of material is a crucial factor. Being able to alleviate cancer patients of disturbing and often slow-recovery procedures, while at the same time improving the quality of diagnosis and disease monitoring seems like a lot to ask. Thankfully, we are blessed with brilliant and dedicated scientists from all around the world who collaborate to make this a reality, sharing their results, knowledge and data.

  Blog advancing-fast-in-the-analysis-of-circulating-tumour-dna

• Cancer Moonshot Biobank

  The National Cancer Institute initiated the Cancer Moonshot Biobank to accelerate research through the collection and distribution of biospecimens for key research efforts. The Biobank will engage with over one thousand cancer patients, being treated with standard-of-care therapies, for longitudinal biospecimen and data collection. Cancer patients will be enrolled into the study from a diverse participant population engaged at medical institutions throughout the U.S. The biospecimens will be distributed to qualified scientists to accelerate research progress. The Biobank program, working closely with Leidos Biomedical, Inc. (LBR), will partner with community hospitals and other medical institutions, designated as Biospecimen Source Sites (BSS), to engage and consent eligible participants and collect biospecimens and associated clinical data; work with a central Biospecimen Core Resource (BCR) to support biospecimen collection, processing and storage activities and perform pathology quality control; work with LBR's Molecular Characterization (MoCha) lab to perform clinical tumor molecular characterization assays and return results to patients and their physicians; and make the biospecimens and associated data available to researchers to accelerate cancer research progress. Return of clinical results, a dedicated Patient and Provider Engagement (PPE) website, electronic informed consent, local participant engagement projects, and an embedded ethical, legal and social issues sub-study will together support patient and provider engagement in the program. Cancer Moonshot Biobank imaging data is being made available in The Cancer Imaging Archive (TCIA) on a release schedule that is coordinated with the program releases of data to dbGaP. The imaging data can be found at the following link: Cancer Moonshot Biobank Imaging

  Study phs002192