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• Genome-wide analysis of genetic risk factors for rheumatic heart disease in Aboriginal Australians provides support for pathogenic molecular mimicry

  Background. Rheumatic heart disease (RHD) following Group A Streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers pro-inflammatory cardiac valve-reactive T-cells. Methods. Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single nucleotide polymorphisms (SNPs) were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. Results. The strongest genetic association was intronic to HLA-DQA1 (rs9272622; P=1.86x10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (OR 1.44, 95%CI 1.09-1.90, P=9.56x10-3) and HLA-DQA1*0103_DQB1*0601 (OR 1.27, 95%CI 1.07-1.52, P=7.15x10-3) were risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P=2.36x10-3) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the two risk haplotypes than the protective haplotype. Conclusions. Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis.

  Study EGAS00001002678

• The Medical Genome Reference Bank: a whole genome data resource of 4,000 healthy elderly individuals.

  Allele frequency data from human reference populations is of increasing value for filtering and assignment of pathogenicity to genetic variants. Aged and healthy populations are more likely to be selectively depleted of pathogenic alleles, and therefore particularly suitable as a reference populations for the major diseases of clinical and public health importance. However, reference studies of the healthy elderly have remained under represented in human genetics. We have developed the Medical Genome Reference Bank (MGRB), a large scale comprehensive whole genome dataset of confirmed healthy elderly individuals, to provide a publicly accessible resource for health related research, and for clinical genetics. It also represents a useful resource for studying the genetics of healthy aging. The MGRB comprises 4,000 healthy, older individuals with no reported history of cancer, cardiovascular disease or dementia, recruited from two Australian community based cohorts. DNA derived from blood samples will be subject to whole genome sequencing. The MGRB will measure genome wide genetic variation in 4,000 individuals, mostly of European decent, aged 60 to 95 years (mean age 75 years). The MGRB has committed to a policy of data sharing, employing a hierarchical data management system to maintain participant privacy and confidentiality, whilst maximizing research and clinical usage of the database. The MGRB will represent a dataset of international significance, broadly accessible to the clinical and genetic research community.

  Study EGAS00001003511

• Non-muscle Invasive Bladder Cancer Molecular Subtypes Predict Differential Response to Intravesical Bacillus Calmette-Guérin

  The recommended treatment for patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. In case of progression to advanced disease, patients must undergo a radical cystectomy with significant morbidity and have a poor clinical outcome. Identifying tumors least likely to respond to BCG can translate into alternative treatments, such as early radical cystectomy or novel targeted or immunotherapies. Here we present molecular profiling of 132 BCG-naive, HR-NMIBC patients, and 44 post-BCG recurrences (34 matched), which uncovered three distinct BCG Response Subtypes (BRS1-3). Patients with BRS3 tumors have reduced recurrence and progression-free survival compared to BRS1-2. BRS3 tumors expressed high EMT-basal markers and had an immunosuppresive profile, which was confirmed with spatial proteomics. Tumors which recurred post-BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive HR-NMIBC patients and the molecular subtypes outperformed guideline recommended risk stratification based on clinicopathological variables. For clinical application, we validated that a commercially approved assay was able to accurately predict BRS3 tumors (AUROC 0.86). Our findings provide a potential clinical tool for improved identification of HR-NMIBC patients at the highest risk of progression, which can be used to select patients for early radical cystectomy or novel subtype-directed therapies.

  Study EGAS00001006879

• H3Africa - Stroke Investigative Research and Education Networks

  Although stroke is a discrete phenotype, it is the clinical culmination of several complex and interacting biological processes, precipitated by various genetic and environmental factors, thereby making ready analyses of its underlying mechanisms a challenge. However, the formulation of successful tailor-made prevention strategies for limiting the immense personal and societal burden of stroke in Sub-Saharan Africa (SSA) is contingent on a better understanding of the predisposing risk factors for stroke in the region, which may not necessarily match the nature of stroke risk factors described among other people on other continents. Indeed, the underlying risk factors for stroke in SSA have hitherto not been comprehensively characterized, and currently there is a paucity of expertise, experience, and infrastructure in genomics and environmental research in SSA, to initiate and sustain such investigation. We seek to establish the Stroke Investigative Research and Education Network (SIREN) as a multidisciplinary collaborative research network of investigators in SSA and the United States collectively focused on exploring ways to promote a better understanding of the genetic and environmental risk factors for stroke among people of African ancestry. SIREN will evaluate unique contributors to stroke in SSA and compare these findings with those in a cohort of African American stroke survivors, all while simultaneously building sustainable capacities in phenomics, biobanking, genomics, biostatistics and bioinformatics for future high-level investigation of stroke and other vascular disease entities in SSA.

  Study EGAS00001007331

• DAC for "Pyjacker identifies enhancer hijacking events in acute myeloid leukemia including MNX1 activation via deletion 7q"

  This is the DAC for the study "Pyjacker identifies enhancer hijacking events in acute myeloid leukemia including MNX1 activation via deletion 7q" of Christoph Plass (c.plass@dkfz.de).

  Dac EGAC50000000472

• Identify disease-related genes

  Raw data (idat file) analyzed by Illumina SNP array for patients in the 1st cohort and the 2nd cohort (51 diseases).

  Study JGAS000703

• Sensitive gene analysis of hereditary cardiovascular disease

  This research aims to identify disease sensitive genes and their gene variants by genome analysis for hereditary cardiovascular diseases.

  Study JGAS000295

• Whole-genome sequencing for 61 early-onset diabetes patients and 174 controls

  This dataset contains 241 paired FASTQ files for 61 early-onset diabetes patient and 174 controls sequenced with MGI Tech DNBSEQ-T10 and DNBSEQ-T7.

  Dataset EGAD50000001450

• PCA Atlas donor genotyping arrays (Axiom UK Biobank v2.0)

  Raw Axiom v2.0 UK Biobank Array CEL files for PCA Atlas donor buffy-coat DNA, used to generate SNP genotypes for demultiplexing single-cell and spatial transcriptomics libraries.

  Dataset EGAD00010002818

• Neuroblastoma Cell Line Circle-seq

  We generated Circle-seq data for 12 neuroblastoma cell lines to describe the landscape of extrachromosomal circular DNA in neuroblastoma.

  Study EGAS00001004796

• WGS files for double minute brain tumor paper.

  Whole Genome Sequencing files accompanying the paper titled "Structure and evolution of double minutes in diagnosis and relapse brain tumors". Please read the paper for more details.

  Dataset EGAD00001004337

• H3Africa H3AChipDesign MalSic

  The dataset includes BAM, FASTQ and decompressed gVCF files for 50 samples from Benin generated for the H3Africa Chip Design Study.

  Dataset EGAD00001004557

• McGill EMC Release 4 in tissue "venous blood" for cell type "CD4-positive, alpha-beta T cell"

  McGill EMC Release 4 in tissue "venous blood" for cell type "CD4-positive, alpha-beta T cell"

  Dataset EGAD00001001280

• Chip-exo and Chip-nexus for five TFs in three colorectal cancer cell lines

  Chip-exo and Chip-nexus for FOXA1, HNF4A, KLF5, MYC, and TCF7L2 in colorectal cancer cell lines LoVo, GP5D, COLO320DM

  Dataset EGAD00001004099

• OncoCis: Annotation of cis-regulatory mutations in cancer

  RNA-seq dataset used for the validation of CDK6 cis-regulatory mutation annotated by OncoCis. NB bam files for manuscript A_Proteomic_Chronology_of_Gene_Expression_through_the_Cell_Cycle_in_Human_Myeloid_Leukemia_Cells are now available at the following link:http://www.ebi.ac.uk/ena/data/view/ERP008483

  Dataset EGAD00001001019

• Whole genome sequencing of 98 tumour-normal pairs for the pancreatic neuroendocrine cancer project

  Whole genome sequencing of 98 tumour-normal pairs for the PAEN-AU pancreatic neuroendocrine cancer project.

  Dataset EGAD00001002684

• Hospital for Sick Children Infant Glioma RNA Sequencing

  Whole transcriptome (n=4) and targetted RNA sequencing (n=15) .bam files of infantile glioma samples reported on at the Hospital for Sick Children

  Dataset EGAD00001005092

• Whole genome sequencing of AML samples at presentation, remission, and relapse

  Whole genome sequencing of AML blood or bone marrow at presentation and remission for 5 patients. Relapse samples are included for 2 patients, totaling 12 WGS BAM files.

  Dataset EGAD00001005120

• T-WGBS for Naive B Cell

  Tagged-WGBS for 3 Naive B Cell samples of the CancerEpiSys-PRECiSe project.

  Dataset EGAD00001005966

• ATAC data for Glioblastoma (EGAS00001003953, H016)

  ATAC-seq data for 2 glioblastoma cell lines (LN229, ZH487), NT and SOX10KD.

  Dataset EGAD00001006544

• Trio Sequencing results for the AnkyrinG MIPS screening study

  Approximately 1000 trio's with varying degrees of cognitive disorders. All samples have been sequenced for the AnkyrinG interactome using MIPS technology. Data is presented as BAM and unfiltered VCF files.

  Dataset EGAD00001006823

• A molecular signature for IL-10-producing Th1 cells in protozoan parasitic diseases

  A molecular signature for IL-10-producing Th1 cells in protozoan parasitic diseases

  Dataset EGAD00001007532

• Human Origins array data for 1510 individuals

  Genotype data typed on the Human Origins array for 1510 individuals published in "Dense sampling of ethnic groups within African countries reveals fine-scale genetic structure and extensive historical admixture."

  Dataset EGAD00001010015

• RNAseq for Patients of NIBIT-M4 clinical trial

  RNAseq for Patients of NIBIT-M4 clinical trial

  Dataset EGAD00001009702

• CUTRUN files for Klco-NUP98 data

  CUTRUN files for paper titled "Fusion oncoproteins and cooperating mutations define disease phenotypes in NUP98-rearranged leukemia"

  Dataset EGAD00001015478