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• Widespread hypertranscription in aggressive human cancers

  Data used to validate RNAmp tool.

  Dataset EGAD00001009285

• mFAST-SeqS estimation of tumor fraction

  Modified Fast Aneuploidy Screening Test-Sequencing System (mFAST-SeqS) was applied to stratify samples based on their overall tumor fraction in cfDNA.

  Dataset EGAD00001006385

• Spatial transcriptomics reveal topological immune landscapes of Asian head and neck angiosarcoma

  Angiosarcomas are rare malignant tumors of the endothelium, arising commonly from the head and neck region (AS-HN) and recently associated with ultraviolet (UV) exposure and human herpesvirus-7 (HHV-7) infection. We examined 81 cases of angiosarcomas, including 47 cases of AS-HN, integrating information from whole genome sequencing, gene expression profiling and spatial transcriptomics (10X Visium). In the AS-HN cohort, we observed recurrent somatic mutations in CSMD3 (18%), LRP1B (18%), MUC16 (18%), POT1 (16%) and TP53 (16%). UV-positive AS-HN harbored significantly higher tumor mutation burden (TMB) than UV-negative cases (p=0.0294). NanoString profiling identified three clusters with distinct tumor inflammation signature (TIS) scores (p<0.001). Spatial transcriptomics revealed topological profiles of the tumor microenvironment, identifying dominant but tumor-excluded inflammatory signals in “immune-hot” cases and immune foci even in otherwise “cold” cases. In conclusion, spatial transcriptomics reveal the tumor immune landscape of angiosarcoma, and in combination with multi-omic information, may improve implementation of treatment strategies.

  Study EGAS00001007083

• Dynamic N6-methyladenosine Epitranscriptomic Landscape in Lung Adenocarcinoma

  Systematically evaluate the global effect of dysregulated m6A regulators on the m6A epitranscriptome in patient tumors, and identify prognostic m6A markers by linking with patients' clinicopathological and outcome information.

  Study EGAS00001005524

• Identification of four new susceptibility loci for testicular germ cell tumour, including variants near GAB2, GSPT1 and ZFPM1

  Genome wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify further SNPs associated with TGCT we conducted a multistage GWAS with a combined dataset of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P = 1.5 x 10-9), 11q14.1 (rs7107174, GAB2, P = 9.7 x 10-11), 16p13.13 (rs4561483, GSPT1, P = 1.6 x 10-8) and 16q24.2 (rs55637647, ZFPM1, P = 3.4 x 10-9). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.

  Study EGAS00001001302

• SECRETO Oral metagenome study

  The main goal of the project is to study the associations between the oral metagenome and young-onset cryptogenic ischemic stroke (CIS). The dataset includes information for n=329 participants who underwent saliva sampling. Participants for the SECRETO Oral study were enrolled between December 2013 and November 2019. Shotgun metagenomic sequencing was performed using the Illumina NovaSeq 6000 platform.

  Study EGAS00001007505

• PCA Atlas Visium spatial transcriptomics data (FASTQs, spaceranger BAMs and Visium mapping tables)

  This dataset contains Visium spatial transcriptomics data for the PCA Atlas study EGAS00001008332. It includes: - Raw Visium FASTQ runs (EGAR00004172272–EGAR00004172283) for all libraries. - spaceranger alignment BAM analyses for those libraries where BAM output was generated. - visium.csv: a slide-level mapping table linking Visium slide samples to EGA sample accessions, sequencing runs/experiments and spaceranger BAM analyses. - visium_tma.csv: a TMA mapping table describing how mini-TMA slides relate slide-level Visium libraries to tissue-level samples/cores. Together these objects provide the raw and aligned Visium data and the technical/biological mappings needed to understand and reuse the spatial transcriptomics component of the PCA Atlas. High resolution histology images are available from the following Zenodo repository, along with additional spaceranger outs for each slide: - https://zenodo.org/records/17411292

  Dataset EGAD00001015796

• The Natural History of Human Prostate Cancer

  Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of 3 men. For each of three different prostates, multiple tumour samples (4, 5, and 3 depending on the case) and one normal tissue sample were whole genome sequenced with a matched blood sample using the Illumiuna HiSeq platform. Tumour samples were sequenced to a target depth of 50X and normals and blood to a target depth of 30X. As of September 2020, some of the studies using these data include: Cooper et al, Nature Genetics 2015 (PMID: 25730763) Wedge et al, Nature Genetics 2018 (PMID: 29662167) Pan-Cancer Analysis of Whole Genomes, Nature 2020 (PMID: 32025007)

  Dataset EGAD00001000689

• Identification Of Pathogenic Mutations And Application Of Polygenic Risk Scores In Early-Onset Diabetes Patients

  Maturity-onset Diabetes of the Young (MODY) presents a diagnostic challenge. In this study we investigate the genetic background of Latvian early-onset diabetes patients, using whole-genome sequencing data. Additionally, we investigate the utility of previously published and available type 1 diabetes (T1D) and type 2 diabetes (T2D) polygenic risk scores in differentiating monogenic diabetes (MODY) from T1D and T2D cases.

  Study EGAS50000000991

• Tissue DNA, WBC DNA and cfDNA (deep-)sequencing of mCRC patients treated with doublet chemotherapy and anti-EGFR in the CAIRO5 study

  This study assessed whether ctDNA based treatment response monitoring could be performed in a tumor tissue-independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC) derived DNA. In total, 183 cfDNA and 49 WBC samples, along with 28 tissue samples, from 52 metastatic colorectal cancer patients participating in the prospective phase III CAIRO5 clinical trial (NCT02162563) were analyzed using the PGDx elio plasma resolve assay.

  Study EGAS00001006695

• Myocardial Applied Genomics Network (MAGNet) Study

  The MAGNet repository includes non-failing samples from organ donors with no history of heart failure and failing samples from explanted hearts of donors receiving a heart transplant. The study protocol was approved by the Institutional Review Board at the University of Pennsylvania, and all patients provided written informed consent to participate.

  Study phs001539

• RNA-seq analysis of midbrain dopaminergic neurons following ZFHX4 knockdown.

  We performed RNA-seq analysis on midbrain dopaminergic neurons derived from induced pluripotent stem cells following lentiviral-mediated knockdown of the transcription factor ZFHX4. Transcriptomic analysis enabled the identification of potential ZFHX4 target genes. Enrichment analysis of the differentially expressed genes was conducted to assess the biological pathways regulated by ZFHX4.

  Study EGAS50000001111

• Meningioma_Exome

  Agilent whole exome hybridisation capture will be performed on genomic DNA derived from Meningioma tumour samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting exome libraries and mapped build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00001000177

• Orphan_Tumour_Study_NB

  The aim of this study is to investigate the transcriptional landscape of human cancer. 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/

  Study EGAS00001003445

• ICARUS-LUNG01-RNAseq

  Bulk RNA-seq was carried out on 20 pairs of frozen tumor biopsies. Differential gene expression (DGE) analyses was conducted, looking at the fold change of gene expression of matched on-T/BL samples in the overall population and, then, separately in responders and non-responders.

  Study EGAS50000000732

• Targeted sequencing about core genes involved in telomere biology in colorectal cancer patients

  We sequenced the coding exons of core genes involved in telomere maintenance using peripheral blood DNA of 192 CRC patients. The primary sequencing data were generated by using Ion Torrent Personal Genome Machine® (PGM™) platform (Life Technologies, Carlsbad, CA, USA).

  Study EGAS00001002977

• Tagmentation-based Whole Genome Bisulfite Sequencing

  We demonstrated the reliability of the tagmentation-based whole genome bisulfite sequencing in direct comparison with the conventional whole genome bisulfite sequencing.

  Study EGAS00001000528

• DUX4 activates novel intergenic transcripts and isoforms in a tissue-specific context

  DUX4, a transcription factor driving zygotic genome activation during the embryonic cleavage stage in mammals, regulates the expression of genic and non-genic elements and modulates chromatin accessibility. Its misexpression in skeletal muscle causes Facioscapulohumeral muscular dystrophy (FSHD). The sporadic expression of DUX4 in FSHD muscle and the limitations of short-read RNA sequencing challenge, however, a comprehensive grasp of its consequences on the muscle transcriptome. Here, leveraging full-length isoform RNA sequencing with short-read RNA sequencing on DUX4-inducible myoblasts, we elucidated DUX4-induced transcriptomic changes within a myogenic context. DUX4 yields a complex transcriptome featuring numerous unannotated isoforms from known and novel loci. Moreover, we observed distinct isoform usage of DUX4 target genes between myogenic and embryonic cleavage states highlighting the distinct differences between DUX4 transcription factor activity in skeletal muscle and during the cleavage stage. We also identified ~1,400 unannotated intergenic isoforms predominantly originating from repetitive elements such as LTRs, LINEs, and SINEs. Integration with available datasets delineates the transcriptional and epigenetic landscape of these loci across myogenic and embryonic backgrounds. Like the cell type-specific isoform production, the usage of DUX4 binding sites at these intergenic loci is in part cell type-specific. Collectively, these findings demonstrate substantial and context-specific transcriptomic alterations induced by DUX4 further enriching our understanding of DUX4-induced muscle pathology.

  Study EGAS50000000503

• Single cell chromatin accessibility profiles from myelofibrosis patients

  To explore how JAK2V617F disrupts cell-fate and the regulatory chromatin landscape of HSCs, we applied GoT-ChA to CD34+ sorted progenitor cells from 21 human primary samples, comprising 18 patients with JAK2V617F-mutated MF (no additional mutations, except for Pt-08), who either had no treatment (n = 12; including three longitudinal samples from a PV patient who progressed to MF) or who were treated with ruxolitinib (n = 6), a JAK1/2 inhibitor. We included a JAK2V617F CH sample (Pt-19) to explore early epigenetic changes, before the onset of overt hematological abnormality.

  Dataset EGAD50000000234

• Genome Sequencing and Variant Calling of HCM Patients with MYH7 Variants

  To investigate potential genetic causes of cardiomyopathy we recruited 48 patients harboring rare MYH7 variants identified from panel-based testing and with a clinical manifestation of cardiomyopathy. Genome sequencing was performed to identify other potential causative variants and genetic modifiers of the cardiomyopathy phenotype, which varied among patients.

  Study phs004024

• 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

• Paired exome and low-coverage genome sequencing of osteosarcoma

  We perform longitudinal genome-sequencing analysis of 12 patients with metastatic or refractory osteosarcoma. The study was approved at the University Hospital Basel, following the approval of the ethical committee for mutational analysis of anonymized samples (“Ethikkommission beider Basel” ref. 274/12). All tumor samples were evaluated by an experienced bone pathologist to confirm the diagnosis.

  Study EGAS00001005199

• Genomic, transcriptomic and epigenomic profiling of GCTB

  Giant cell tumor of bone is a rare bone neoplasm driven by oncogenic hotspot G34W/L/V mutations in the non-canonical histone variant H3.3. This study provides primary data of genomic (WGS), transcriptomic (RNA-seq) and epigenomic (histone mark ChIP-seq, WGBS, ATAC-seq) profiling of primary GCTB samples from several cohorts in Germany and Korea. We confirm the H3.3-G34 mutations as sole genetic drivers of GCTB, and describe the epigenetic alterations in mutant GCTB stromal cells.

  Study EGAS00001003730

• LCM-ATACseq on human lung macrophages

  In this study we employed Laser Capture Microdissection (LCM) for the multimodal profiling of lung macrophages cell populations as a function of location within the healthy tissue. In detail, macrophage mini-bulks (~100 cells) were collected from 4 healthy human donors in 5 different locations of the airways (a total of 20 biopsies), including parenchyma (L1 – lower left lobe (LLL); L6 – 80% distance from LLL tip), trachea (L2), bronchi (L3 – 1st/2nd generation; L5 – 3rd/4th generation), and processed for ATAC-seq.

  Study EGAS00001006167

• Targeted sequencing of breast cancers with germline BRCA1/2 mutations

  Breast cancer is the most prevalent cancer in women, where a germline predisposition plays a substantial role. However, the effects of pathogenic germline variants on accompanying breast cancers have not been fully characterized in terms of somatic alterations. We obtained tumor samples from 30 patients with pathogenic germline variants in BRCA2 (n = 25) and BRCA1 (n = 5), as well as an additional 30 patients without pathogenic germline mutations, in which somatic mutations in common breast cancer drivers and CNAs were analyzed using targeted panel sequencing.

  Study EGAS00001004182