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• Analysis of Cell-Free DNA to Predict Outcome to Bevacizumab Combination Therapy in Metastatic Colorectal Cancer Patients

  This dataset includes FASTQ files of low coverage whole genome sequencing of normal tissue (n = 8), tumor tissue (n = 55) and cell free DNA from plasma samples (n=101) from patients with metastatic colorectal cancer treated with bevacizumab. A total of 164 samples are present from two different cohorts. The first batch of samples (n = 139, sample names sAPD302T until sAPD502_P0) were collected from the AC-Angiopredict Phase 2 trial (NCT01822444), the second batch of samples (n = 25m, sample names sAPD503_P0 until sAPD527_P0) were collected from the UMM cohort.

  Dataset EGAD50000000176

• Identification of the cause of juvenile parkinsonism in a case_SYNJ1

  This study aimed to elucidate the genetic causes underlying the Juvenile Parkinsonism diagnosed in a girl using whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification. As a result, a homozygous missense mutation SNP T/C (rs2254562) in SYNJ1 and alteration in metabolism were identified.

  Study EGAS00001007686

• LongVar low-coverage data

  This dataset includes sequencing data from participants of the LongVar study. Specifically, it comprises low-coverage whole genome sequencing (WGS) data which was derived from cell-free DNA from blood samples. These data were generated to compare imputation accuracy. 133 individuals agreed to share their data, and are healthy volunteers.

  Study EGAS50000001114

• Heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer

  A mutation accumulation experiment in colorectal cancer (CRC) derived tumoroids, aimed at measuring the spontaneous rates of accumulation of new single-nucleotide sequence variations in seven microsatellite stable CRCs and one microsatellite unstable CRC. Mutations accumulated over six+six months were identified via whole genome sequencing of clonal tumoroids.

  Study EGAS50000000284

• scRNA-seq data of Anti-Her2-CAR T cells treated with immunomodulatory metabolites

  Anti-Her2-CAR T cells produced from T cells derived from healthy human donors were treated with DMSO (control) or either of the immunomodulatory metabolites indole‐3‐carboxaldehyde (ICA), valeric acid (VA) and isovaleric acid (IVA) to assess effects on CAR T cell function. scRNA-seq libraries were generated on a 10X Chromium controller with On-Chip-Multiplexing. The individual samples in a library are distinguished during analysis on the single-cell level via the cell barcode class.

  Dataset EGAD50000002012

• Single-cell RNA sequencing of metastatic colorectal cancer patient-derived xenografts treated with cetuximab

  Single-cell RNA sequencing was performed on a cetuximab-sensitive metastatic colorectal cancer (mCRC) patient-derived xenograft (PDX) model. The objective of this analysis was to assess whether the transcriptional patterns identified in the single-cell RNA-seq data of matched organoids were preserved in the in vivo context.

  Study EGAS50000001459

• Building a Database of Genomic Structural Variants in Japanese population

  Epstein-Barr virus immortalized B-lymphoblast cell lines were obtained through the Japanese Collection of Research Bioresources (Japanese B cell DNA bank), National Institutes of Biomedical Innovation, Health and Nutrition, and cultured at UNITECH Co., Ltd. We extracted genomic DNAs, sequenced them using Nanopore PromethION, and analyzed genomic structural variations.

  Study JGAS000580

• Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity

  We performed SNP and copy number variation (CNV) association analyses in 1,509 children with obesity at the extreme tail (>3 s.d. from the mean) of the BMI distribution and 5,380 controls. The control samples were made available from the EGA with accession numbers EGAD00000000021 and EGAD00000000023.

  Study EGAS00001000878

• Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19

  Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of patients infected with influenza and a cohort of patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines.

  Study EGAS00001005971

• Smart-seq3 scRNA-seq of cells from primary (OV2295) and metastatic (OV2295R2) high-grade serous ovarian cancer cell-line

  In this project, single cells extracted from two high-grade serous ovarian cancer cell-lines, one primary (OV2295) and one metastatic (OV2295R2), where split into two 384 well plates and libraries were prepared using Smart-seq3 single cell RNA sequencing (Hagemann-Jensen et al, 2020).

  Study EGAS00001006868

• bulk TCR-seq data IMCISION

  We performed bulk TCR sequencing (Adaptive Biotechnologies, Seattle, WA) on peripheral blood monocytic cells (PBMCs) from 9 HNSCC patients enrolled in the IMCISION trial (Vos et al. 2021) that responded to anti-PD-1 and anti-CTLA4 combination immunotherapy. DNA was extracted from PBMCs that were isolated from pre-treatment and on-treatment blood.

  Study EGAS00001007367

• Liquid-based genomic profiling in high-risk localized prostate cancer.

  In this study, we evaluated the feasibility and performance of tissue and liquid-based genomic profiling in patients with high-risk localized prostate cancer. Genomic DNA from 12 FFPE tissue samples and cell-free DNA from 27 plasma samples were analyzed using Illumina TruSight Oncology (TSO) 500 panels.

  Study EGAS50000001712

• Somatic L1 retrotransposition dynamics in high-grade serous ovarian cancer

  Somatic L1 retrotransposition was mapped in high-grade serous carcinoma (HGSC) tumors using LDI-PCR/Nanopore-seq method. This method identifies somatic L1 insertions originating from two active L1 loci at chr22q12.1 and chrXp22.2. Multiple tumors from same patient were utilised to understand L1-mediated intrapatient heterogeneity.

  Study EGAS50000001198

• Integrative analysis reveals a macrophage-predominant, immunosuppressive immune microenvironment and subtype-specific therapeutic vulnerabilities in advanced salivary gland cancer

  Background Salivary gland cancers (SGC) are rare and heterogeneous malignant tumors. Advanced SGC lack established treatment options and show poor response to immunotherapy. Here, an integrative multi-omics analysis in a large cohort of advanced SGC revealed insights into the tumor immune microenvironment (TIM) and distinct mechanisms of immune evasion. Methods A total of 104 patients with recurrent/metastatic SGC from the DKTK MASTER program were included in this study. Whole-exome or whole-genome sequencing and RNA-sequencing was performed on fresh frozen tumor tissue. The tumor immune microenvironment was analyzed using CIBERSORT deconvolution analysis and immune gene expression scores in bulk RNA-sequencing data. Single-nuclei sequencing and immunohistochemistry analyses were performed in selected samples. Results were validated in bulk RNA-sequencing data of a previously published independent dataset. Results Bulk transcriptome analysis revealed an immune-deserted TIM in the majority of advanced SGC samples. Immune exclusion was most prominent in adenoid cystic carcinoma (ACC) subgroup 1 exhibiting a downregulation of the antigen processing machinery. Only a small subset of advanced SGC, including few adenoid cystic carcinoma, exhibited T-cell inflammation, which was correlated with tumor mutational burden in Non-ACC samples. Subtype specific expression of immune checkpoints as well as cancer testis antigens were identified with prominent expression of VTCN1 in luminal cells within ACC. Single-cell RNA-sequencing and bulk RNA-seq deconvolution analysis validated immune cell exclusion and revealed a TIM that was dominated by M2 macrophages across SGC subtypes. Among evaluable patients treated with immune checkpoint inhibitors, a high T-cell to macrophage ratio was associated with clinical benefit. Conclusions These data support biomarker-based development of immune-checkpoint inhibition and the development of novel immune-checkpoint inhibitors and cellular therapies in SGC.

  Study EGAS50000000809

• Investigating Genetics in Suspected Congenital Syndromes

  We employed forward and reverse genetics to identify individuals with heterozygous JAK1 variants associated with autoimmune and inflammatory diseases. We first recruited six unrelated probands and seven affected family members presenting with a range of autoimmune and inflammatory conditions. Whole exome sequencing revealed 4 different variants spanning all domains of the JAK1 protein: FERM domain (chr1: 64873438-G>A; c.415C>T; p.E139K), SH2 domain (chr1: 64855641-G>A; c.1516C>T; p.R506C), pseudokinase domain (chr1: 64845529-C>T; c.2099G>A; p.S700N, and kinase domain (chr1: 64838479-C>T; c.2953G>A; p.V985I). We then performed a systematic review of electronic health records of the BioME BioBank database and identified 43 additional individuals with at least one of these JAK1 variants. Comparing variant-positive and variant-negative individuals, our study revealed increased occurrences of autoimmunity, atopy, colitis, and dermatitis in patients harboring these JAK1 gain-of-function variants. We have deposited in dbGaP the whole exome sequencing files of the 43 patients identified in the BioME biobank, as well as their phenotype information.

  Study phs003453

• CCDG CVD: VIRGO - Variation in Recover-Role of Gender on Outcomes of Young Acute Myocardial Infarction (AMI) Patients

  The VIRGO study is a four year research project funded by the NHLBI to study young women and men with heart attacks. A total of 2,000 women who are 18 - 55 years of age and a smaller comparison group of 1,000 similarly aged men will be enrolled in this multi-site observational study from approximately 120 different hospitals across the country. Young women have a much greater risk of dying after an acute myocardial infarction (AMI) than similarly aged men. Their mortality risk is markedly higher than that of young men, and limited data on young minority women suggest that they may have the highest risk of any young subgroup. Findings from the small number of published studies of young women with ischemic heart disease suggest that the biology, epidemiology, care, and outcomes of this group are distinct from those of men. To date, there have been no large studies of this population, even as the death toll is comparable to that from breast cancer in this country. This study will help researchers identify key factors that influence recovery from a heart attack and potentially improve the care and outcomes of young women and men with AMI. Specific Aims: To investigate the excess risk in young women with AMI and to identify key demographic, clinical, metabolic, psychosocial, health care delivery, and biological determinants of prognosis, we propose a national, prospective, observational study of 2,000 women who are 55 years or younger with AMI and a smaller comparison group of 1,000 men. Our prior work and preliminary studies indicate that the sex differences are most prominent in this age group and suggest that by 1 year after discharge, there are substantial sex differences in outcomes. We will also develop risk stratification tools that will help clinicians to identify young women with the highest and lowest risk. Specific Aim 1: Determine sex differences in outcomes following AMI. Specific Aim 2: Determine sex differences in the prevalence and prognostic importance of demographic, clinical, and psychosocial risk factors. Specific Aim 3:Determine sex differences in quality of care. Specific Aim 4: Determine sex differences in the prevalence and prognostic importance of selected biochemical biomarkers following AMI. These samples have been whole genome sequenced as part of the NHGRI's Center for Common Disease Genetics at the Broad Institute.

  Study phs001259

• Phenotypic characterization and prognostic impact of CD103+ tissue-resident memory T cells in diffuse large B cell lymphoma

  Tissue-resident memory T (TRM) cells are a population of memory T cells that stably occupy tissues and play a key role in immunosurveillance, having been linked to favorable survival outcomes in various solid tumors. While TRM cells have been identified in lymph nodes, their phenotype and prognostic significance in B-cell non-Hodgkin lymphoma (B-NHL), including diffuse large B-cell lymphoma (DLBCL), remains poorly characterized. The frequency of CD103 expressing T cells in patient samples with DLCBL was quantified by immunofluorescence (IF) staining of tissue biopsies (n=306) and flow cytometry (n=252) of cell disaggregates, and linked with clinical outcome. The phenotype of TRM cells was characterized by spectral flow cytometry (n=10 DLBCL and 2 reactive lymph node (rLN) samples) and single-cell RNA sequencing (scRNAseq) (n=12 aggressive B cell lymphomas and 4 rLN samples). An additional 51 samples from an external dataset were included to verify the single cell transcriptome findings. The flow cytometry and scRNAseq findings in DLBCL were extrapolated to additional B-NHL entities. Through analysis of these datasets we were able to characterize CD103+ TRM-like cells in DLBCL and other B-NHL entities and identified them to represent a prognostically favorable population with an activated/cytotoxic T cell phenotype.

  Study EGAS50000000943

• ProstOmics - Spatial Transcriptomics

  Spatial transcriptomics data (ST) from 32 human prostate tissue samples originating from 8 prostate cancer patients (5 patients with post-surgery relapse). The ST data was acquired using the Visium Spatial Gene Expression kit which resulted in over 20 000 spatially defined spots for the 32 tissue samples. The raw transcriptomics data is RNA-seq. The individual samples have information on patient origin and sample type (cancer, cancer-adjacent field-effect normal or normal sample far from cancer). Each ST spot has metadata such as sample origin, histology class (stroma, normal epithelium, cancer of various grading etc), number of cells and estimated cell type fractions. Patient metadata include information of age at surgery, time (months) until reported relapse, total follow-up time, pre-surgery PSA, post-surgery T-stage and metastasis status.

  Dataset EGAD50000000603

• Identification of immune mechanisms associated with the high rate of relapse in patient with visceral leishmaniasis and HIV co-infection

  RNA-seq transcriptomics of whole blood samples from longitudinal follow-up of a cohort of visceral leishmaniasis (VL) patients with and without HIV coinfection, from active disease through apparent cure and potential relapse. Analysis will identify potential correlates of relapse to identify immune mechanisms underlying the high rate of relapse in HIV/VL coinfection. 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/ .

  Dataset EGAD00001008361

• Sequence Data from the phase 2 PrE0505 trial of Durvalumab with First Line Platinum-Pemetrexed for Unresectable Pleural Mesothelioma

  Dataset comprises of 84 bam files from exome sequencing data, including 40 tumor-normal pairs and 4 normal files. Each sample is numbered by the patient case ID such as 135, 156 and so on. The filenames are suffixed with "_tumor" and "_normal" to indicate tumor and normal bam files respectively.

  Dataset EGAD00001008016

• Massachusetts General Hospital (MGH)/Broad Hurthle cell carcinoma whole exome sequencing study

  In this study, we performed whole-exome sequencing of 41 patients with Hurthle cell carcinoma, a thyroid cancer variant with abundant mitochondria. We were able to identify recurrent somatic mutations in both the nuclear and mitochondrial genomes of Hurthle cell carcinoma. Our study identifies mutations in DAXX (GeneID: 1616), TP53 ( GeneID:7157), NF1(GeneID:4763) , NRAS (GeneID:4893), CDKN1A (GeneID:1026), ARHGAP35 (GeneID:2909), the TERT (GeneID:7015) promoter, and mitochondrial-encoded complex I genes to be candidate driver events in Hurthle cell carcinoma. Furthermore, copy number analysis revealed widespread chromosomal losses, resulting in loss-of-heterozygosity and a near-haploid state, to be a defining feature of these tumors. Finally, by analyzing locoregional recurrences and metastases, we were able to identify that widespread chromosomal losses and mitochondrial complex I mutations appear to be early driver events that are selected during clonal evolution.

  Study phs001580

• mRNA and T cell receptor sequencing of patients with Pandemrix-associated narcolepsy type 1

  Increased risk of Narcolepsy type 1 (NT1) was reported among children and adolescents vaccinated with AS03-adjuvanted pandemic influenza A vaccine (H1N1; Pandemrix®). We hypothesized that viral T cell epitope(s) in Pandemrix mimicked self-epitope(s), and that recognition of these cross-reactive epitopes contributed to disease-specific autoimmunity. We demonstrate that pediatric, Pandemrix-associated NT1 patients had enhanced T-cell immunity against dominant T-cell epitopes of Pandemrix vaccine viral proteins neuraminidase (NA) and nucleoprotein (NP), and also responded against a self-epitope in brain-expressed protein-O-mannosyltransferase 1 (POMT1). Here, the gene expression profiles and TCR repertoire of PBMC from patients and healthy controls were compared. PBMC samples were stimulated with peptides NA-175-189 or POMT1-675-589, and bulk RNA isolated and sequenced (RNAseq and TCRseq).

  Study EGAS00001004886

• Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial

  In HER2-positive breast cancer, clinical outcome and sensitivity to HER2-targeted therapies are influenced by both tumor and microenvironment features. However, we are currently unable to depict the molecular heterogeneity of this disease with sufficient granularity. Here, by performing gene expression profiling in HER2-positive breast cancers from patients receiving adjuvant trastuzumab in the ALTTO clinical trial, we identified and characterized five molecular subtypes associated with the risk of distant recurrence: immune-enriched (IM), proliferative/metabolic-enriched (P/Met), mesenchymal/stroma-enriched (Mes/S), luminal (LUM), and ERBB2-enrichedERBB2-dependent (ERBB2-EERBB2-D). We next validated the biological profiles of the subtypes and explored their prognostic/predictive value in external cohorts, namely the NeoALTTO trial, SCAN-B, I-SPY2, METABRIC and TCGA. IM tumors presented better survival outcomes, in contrast to Mes/S and P/Met tumors, while LUM tumors and ERBB2-EERBB2-D were characterized by low and high rates of pathological complete response, respectively. Of note, these molecular subtypes provide the rationale for treatment approaches leveraging the heterogeneous biology of HER2-positive breast cancer.

  Study EGAS50000000525

• The Ovarian Cancer Association Consortium OncoArray genome-wide association study

  A custom Illumina genotyping array, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis as described in PMID:27697780.The array was used to genotype ovarian cancer cases and controls from multiple studies participating in the Ovarian Cancer Association Consortium, of which 54,747 passes QC.An initial principal components analysis was carried out using a method described in PMID:27697780 to assign subject to intercontinental ancestry groups: “European”, “African”, “Asian” and "Other". Within ancestry principal components analysis was carried using a set of ~33k unlinked markers. Subsequent analyses were adjusted for the ancestry specific PCs: 9 Eur, 10 Asian, 1 African and 6 Mixed. These PCs are included in the imputed dataset phenotypes file

  Study EGAS00001002305

• Japan PBC-GWAS Haplotype Study

  Primary biliary cholangitis (PBC) susceptibility loci have largely been discovered through single SNP association testing. In this study, we report genic haplotype patterns associated with PBC risk genome-wide in two Japanese cohorts. Among the 74 genic PBC risk haplotype candidates we detected with a novel methodological approach in a discovery cohort of 1,937 Japanese, nearly two-thirds were replicated (49 haplotypes, Bonferroni-corrected P<6.8x10-4) in an independent Japanese cohort (N=949). Along with corroborating known PBC-associated loci (TNFSF15, HLA-DRA), risk haplotypes may potentially model cis-interactions that regulate gene expression. For example, one replicated haplotype association (9q32-9q33.1, OR=1.7, P=3.0x10-21) consists of intergenic SNPs outside of the human leukocyte antigen (HLA) region that overlap regulatory histone mark peaks in liver and blood cells, and are significantly associated with TNFSF8 expression in whole blood. We also replicated a novel haplotype association involving non-HLA SNPs mapped to UMAD1 (7p21.3; OR=15.2, P=3.9x10-9) that overlap enhancer peaks in liver and memory Th cells. Our analysis demonstrates the utility of haplotype association analyses in discovering and characterizing PBC susceptibility loci.

  Study EGAS00001002915