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• BLUEPRINT: RNA-seq of progenitor cells

  Data supporting the paper Transcriptional diversity during lineage commitment of human blood progenitors

  Dataset EGAD00001000745

• Prediction of HLA genotypes using NGS data

  High-precision human leukocyte antigen (HLA) genotyping is crucial for anti-cancer immunotherapy, but existing tools predicting HLA genotypes using next-generation sequencing (NGS) data are insufficiently accurate.

  Study EGAS00001005274

• National Heart, Lung, and Blood Institute SNP Health Association Asthma Resource Project (SHARP)

  SNP Health Association Resource (SHARe) Asthma Resource project (SHARP) is conducting a genome-wide analysis in adults and children who have participated in National Heart, Lung, and Blood Institute's clinical research trials on asthma. This includes 1041 children with asthma who participated in the Childhood Asthma Management Program (CAMP), 994 children who participated in one or five clinical trials conducted by the Childhood Asthma Research and Education (CARE) network, and 701 adults who participated in one of six clinical trials conducted by the Asthma Clinical Research Network (ACRN). There are three study types. The longitudinal clinical trials can be subsetted for population-based and/or case-control analyses. Each of the childhood asthma studies has a majority of children participating as part of a parent-child trio. The ACRN (adult) studies are probands alone. Control genotypes will be provided for case-control analyses.

  Study phs000166

• Cancer Affected Patients - Data Access Committee

  Access to the cancer cohort is made available by completing the data access agreement for review by the data access committee and will be granted to qualified investigators for appropriate use. Individuals requesting access to the data need to comply with the terms of a Data Access Agreement (DAA) and are requested to use the data only in approved and ethical ways.

  Dac EGAC50000000037

• Copy-Number Analysis of Understudied Black Women Ovarian Cancers

  Two general types of genetic alterations drive cancer progression: mutations and copy number alterations (CNAs). With the exception of p53, single nucleotide variant mutations (here, simply "mutations") are not drivers of 80% of tumors within the most frequent and deadly histotype of ovarian cancer: serous ovarian cancer (SOC). Rather, CNAs are more prevalent in SOC than any other cancer type studied by phs000178 The Cancer Genome Atlas (TCGA). Fully two-thirds of genes are altered by CNAs in the average SOC. Bioinformatic methods have shown that these CNAs modulate specific molecular pathways, such as autophagy, and this finding enabled effective pathway-targeted therapies1. Unfortunately, TCGA ovarian cancer data lacks racial diversity. Only 6% of SOC tumors (n=32) studied are from African origin. Black women diagnosed with ovarian cancer are more likely to die from their disease than white women. Five-year survival after diagnosis is 31% among blacks versus 42% among whites, and this disparity is seen in every age group and tumor stage distribution. Dr. Kelemen examined data from 365 white and 95 black ovarian cancer patients from the Hollings Cancer Center (HCC) Cancer Registry between 2000 and 2015 and found that black women had an 81% higher risk of death after diagnosis compared to white women (HR 1.81, 95% CI 1.35-2.43), independent of diagnosis center (98% were treated at HCC but half were diagnosed elsewhere), tumor stage, histology, extent of residual tumor remaining following surgery, insurance status, smoking, type of treatment for ovarian cancer, and age-adjusted Charlson comorbidity index. This disparity remained even when restricted to women who received the standard of care, surgery-chemotherapy sequence (HR 1.79, 95% CI 1.10-2.89). Despite receiving the same treatment, black race was still associated with inferior survival. A similar disparity has been reported by others, indicating that the HCC experience is representative of national data. Here, an additional set of high-grade serous ovarian cancer primary tumors were acquired from biorepositories with a focus on expanding data originating from African American women. Data were analyzed for copy-number alterations using exome sequencing and control-FREEC software.

  Study phs002313

• GWAS for IgA Nephropathy

  IgA nephropathy (IgAN) is a common form of immune-mediated glomerulonephritis characterized by glomerular deposition of IgA-containing immune complexes and manifesting with hematuria, proteinuria, and often kidney failure. This dataset is from a genome-wide association study (GWAS) designed to identify novel genetic risk loci for IgAN. In this dataset, seven cohorts were genotyped by Illumina Multi-Ethnic Global Array, consisting of 3,337 IgAN cases and 2,177 healthy controls of European and East Asian ancestries. Three of the provided cohorts were genotyped by Illumina HumanImmuno Chip, which are composed of 2007 cases of IgAN of European ancestry. These cohorts were used in the GWAS meta-analysis, as described in the manuscript entitled "GWAS defines pathogenic signaling pathways and prioritizes drug targets for IgA nephropathy" (Nature Genetics 2022, in press).

  Study phs000431

• Providing safe access to sensitive human data across borders: Federated EGA becomes a reality

  Enabling discovery and access to sensitive data across national boundaries is vital for improving human health. It enables more powerful and efficient research by increasing the volume and diversity of data available for analysis. It allows us to better understand the causes of diseases – cancer, rare diseases, infectious diseases like COVID-19 – and develop new medicines and treatments. Sensitive human omics data are typically generated by research initiatives and shared using specialist repositories which provide services for data submission, discovery, and access. The EGA is one such repository. Established in 2008 at EMBL’s European Bioinformatics Institute (EMBL-EBI) in the UK, since 2012 the EGA (“Central EGA”) has been jointly managed by EMBL-EBI and the Centre for Genomic Regulation (CRG) in Spain. Many countries have emerging personalised medicine programmes which generate data from national initiatives. These programmes are driving a transition in human genomics from being research-driven to receiving funding through healthcare. Data generated in a clinical context are subject to stricter governance than research data and must follow national data protection legislation. To solve these challenges, the Federated EGA provides a network of connected resources to enable transnational discovery of and access to human omics data for research, while also respecting jurisdictional data protection regulations. In this way, the Federated EGA infrastructure supports the goals of European initiatives such as the 1+ Million Genomes initiative (1+MG), the European Health Data Space, and a number of EU-funded 1+MG implementation projects including Beyond 1 Million Genomes. The Federated EGA is made up of “Nodes” – typically nationally funded and operated – which store and manage data locally while allowing global discovery within the Federated EGA network. Since 2016, multiple parallel efforts, supported by ELIXIR and other transnational and national initiatives, have created technical and legal frameworks for establishing the Federated EGA. In 2022, the first five Nodes – Finland, Germany, Norway, Spain, and Sweden – officially joined the Federated EGA by signing Federated EGA Collaboration Agreements with Central EGA. The Finnish FEGA Node is operated by CSC - IT Center for Science and provides data management services according to national laws and the requirements of the EU General Data Protection Regulation (GDPR). These services provide tools and support for the whole life-cycle of sensitive research data from collating to analysis, publication, and authorised re-use. The development of the services has been a joint effort with the other Nordic nodes within NeIC's Tryggve and Heilsa projects, and funded by Finnish Ministry of Education and Culture and projects coordinated by ELIXIR Finland. Read more about Finnish FEGA signing. The German Human Genome-Phenome Archive (GHGA) strives to provide a national infrastructure as well as an ethical and legal framework that balances FAIR omics data usage and data protection needs for Germany. As a Germany-wide consortium funded by the German Research Foundation under the umbrella of the NFDI association, GHGA combines the expertise of 21 universities and research institutions to form a federated national infrastructure. Read more about GHGA signing. The German Human Genome-Phenome Archive (GHGA) strives to provide a national infrastructure as well as an ethical and legal framework that balances FAIR omics data usage and data protection needs for Germany. As a Germany-wide consortium funded by the German Research Foundation under the umbrella of the NFDI association, GHGA combines the expertise of 21 universities and research institutions to form a federated national infrastructure. Read more about GHGA signing. In Norway, a key component of the infrastructure is the services of The Sensitive Data Service (TSD) offered by USIT at University of Oslo. The Federated EGA Norway Node is developed by ELIXIR Norway and operated by the University of Oslo as the responsible legal entity. Core software modules are developed jointly with the other Nordic nodes in the NeIC Tryggve and Heilsa projects. Read more about FEGA Norway signing. The Spanish FEGA (es-FEGA) is a national service for storing sensitive biomedical data in Spain. Supported by the Spanish Institute of Bioinformatics (INB) in collaboration with Central EGA, sensitive research datasets are primarily hosted at the Barcelona Supercomputing Centre facilities. The Swedish Sensitive Data Archive is a secure data archive and sharing platform for sensitive datasets. It was developed by the National Bioinformatics Infrastructure Sweden (NBIS) in collaboration with other Nordic ELIXIR Nodes through the Tryggve and Heilsa projects funded by NeIC and coordinated with Central EGA through ELIXIR. Read more about the Swedish Node signing. The Swedish Sensitive Data Archive is a secure data archive and sharing platform for sensitive datasets. It was developed by the National Bioinformatics Infrastructure Sweden (NBIS) in collaboration with other Nordic ELIXIR Nodes through the Tryggve and Heilsa projects funded by NeIC and coordinated with Central EGA through ELIXIR. Read more about the Swedish Node signing. By providing a solution for secure and efficient management of human omics data, the Federated EGA aims to foster data reuse, enable reproducibility, accelerate biomedical research, and improve human health. Find out more Interested in setting up your own Federated EGA Node? Check out the FEGA Onboarding Knowledge Base for more information. The ELIXIR Federated Human Data Community is a great entry point for anyone interested in learning more about the Federated EGA. You can: Join the ELIXIR Federated Human Data Community mailing list (select “Human Data”) Attend the ELIXIR Federated Human Data Community calls

  Blog safe-access-to-sensitive-human-data-federated-ega

• Single-cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

  GABAergic interneurons are essential for neural circuit function and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and ultimately therapeutic cell replacement. We used a protocol for generating cortical interneurons from hESCs and analyzed the properties and maturation timecourse of cell types using single-cell RNAseq (data available at GEO under: GSE93802 on March 10 2017). Transcriptomic profiles of the hESC-derived interneurons were compared to several different populations of cells from mid-gestation human neocortex that showed differing levels of PAX6 and SOX2 expression. For this study, 104 samples of 100 human neocortical cells each, have been sorted based on SOX2 and PAX6 expression, mRNA recovered from the fixed cells by FRISCR, and transcriptomic profiles generated by SmartSeq2. The RNA-seq data from the 104 100-cell samples is included in this dbGaP study.

  Study phs001276

• NHLBI TOPMed: Genome-Wide Association Study of Adiposity in Samoans

  The individuals sequenced here represent a small subset of the parent study (described below) and were carefully selected for the purpose of creating a Samoan-specific reference panel for imputation back into the parent study. The INFOSTIP algorithm of Gusev et. al. (2012) (PMID: 22135348) was used to optimally choose the individuals for sequencing. The research goal of the parent study (dbGaP ID phs000914) is to identify genetic variation that increases susceptibility to obesity and cardiometabolic phenotypes among adult Samoans using genome-wide association (GWAS) methods. DNA from peripheral blood and phenotypic information were collected from 3,119 adult Samoans, 23 to 70 years of age. The participants reside throughout the independent nation of Samoa, which is experiencing economic development and the nutrition transition. Genotyping was performed with the Affymetrix Genome-Wide Human SNP 6.0 Array using a panel of approximately 900,000 SNPs. Anthropometric, fasting blood biomarkers and detailed dietary, physical activity, health and socio-demographic variables were collected. We are replicating the GWAS findings in an independent sample of 2,500 Samoans from earlier studies. After replication of genomic regions and informative SNPs in those regions, we will determine sequences of the important genes, and determine the specific genetic variants in the sequenced genes that are associated with adiposity and related cardiometabolic conditions. We will also identify gene by environment interactions, focusing on dietary intake patterns and nutrients.

  Study phs000972

• Acquisition_of_additional_mutations_drives_accelerated_progression_of_NPM1_positive_CMML_to_AML_

  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/We performed exome sequencing on serial samples from a patient with CMML who progressed to AML. The exome sequencing suggests that NPM1, TET2 and DNMT3a mutations were present in the dominant clone in the CMML sample and that NRAS is a new subclonal mutation in the AML sample. Diagnostic data shows the presence of a FLT3-ITD mutation in the AML sample, which is likely to have driven progression. Here we are performing re-sequencing of the putative driver and some passenger mutations which appear to be in the same clone to validate these mutations and to verify the relative quantification of these abnormalities .

  Study EGAS00001000619