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• TCR sequencing of head and neck cancers

  This data contains the TCR-beta sequences of 10 head and neck squamous carcinomas and 19 nasopharyngeal carcinomas. The library preparation method is a customised targeted amplification of the VDJ regions and is sequenced on the Illumina Miseq.

  Dataset EGAD00001007917

• Machine Learning Signal Enrichment for Ultrasensitive Plasma Tumor Burden Monitoring

  In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).

  Study EGAS00001007451

• Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring

  In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by 300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer (NSCLC) and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables de novo mutation calling in melanoma and small cell lung cancer (SCLC) without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).

  Study EGAS00001007545

• Human genomic and phenotypic synthetic data for the study of rare diseases

  The purpose of this dataset is to facilitate development of technical implementations for rare disease data integration, analysis, discovery, and federated access. This synthetic dataset includes clinical and genomic data from 6 rare disease cases. It consists of 18 whole genomes (6 index cases with their parents) which have genetic background based on public human data sequenced in the context of the Illumina Platinum initiative (Eberle, MA et al. (2017)) and made available by the HapMap project (https://www.genome.gov/10001688/international-hapmap-project). In each of the cases, real causative variants correlating with the phenotypic data provided were spiked-in. The cases included in this synthetic dataset correspond to the following type of disorders: CASE 1- Congenital myasthenic syndrome (Autosomal Dominant -de novo variant) CASE 2- Macular dystrophy (Autosomal Dominant) CASE 3- Muscular dystrophy (Autosomal Recessive-compound heterozygous variants) CASE 4- Mitochondrial disorder (Autosomal Recessive-consanguineous case - homozygous variant) CASE 5- Breast cancer (Autosomal Dominant) CASE 6- Similar as case 1 for patient matchmaking tests: Congenital myasthenic syndrome (Autosomal Dominant-de novo variant) For each case you will be able to download the following data: clinical information (phenopackets per individual and pedigree per family), raw genomic data (FASTQ and BAMs) and processed genomic data (vcfs). When using the data, the following should be acknowledged: the RD-Connect GPAP (https://platform.rd-connect.eu/), EC H2020 project EJP-RD (grant # 825575), EC H2020 project B1MG (grant # 951724) and Generalitat de Catalunya VEIS project (grant # 001-P-001647).

  Study EGAS00001005702

• scRNAseq of aplastic anemia and healthy immune cells co-cultured with autologous HSPCs

  This dataset contains 8 batches of bone marrow or peripheral blood cells of patients with aplastic anemia and bone marrow cells of healthy controls. The samples from different experimental conditions have been multiplexed with Totalseq-C antibodies (feature barcoding). To demultiplex the samples, see instructions in 10.5281/zenodo.2590196 and https://github.com/janihuuh/aa_manu. Each sample is analysed with Chromium V(D)J and 5' Gene Expression Platform v2 (10X Genomics). The raw data includes fastq files for Gene expression, feature barcodes and V(D)J Expression. The processed data have been deposited in the ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress).

  Dataset EGAD00001012120

• Genome-Wide Pleiotropy Scan Across Multiple Cancers

  A whole-exome sequencing (WES) study was conducted in 3,233 cases diagnosed with multiple primary cancers and 3,229 matched cancer-free controls (90% non-Hispanic white, 3% African-American, 3% East Asian, and 4% Latino) selected from individuals in the Kaiser Permanente Research Bank (KPRB) who were members of the Kaiser Permanente Northern California (KPNC) health plan. Cancer-free controls were matched to cases on age at specimen collection (within 2 years), sex, genotyping array (which matched on self-reported race/ethnicity), closest distance using the first two principal components for genetic ancestry, and reagent kit. Cases and controls were drawn from two prospective KPRB cohorts: the Research Program on Genes, Environment and Health (RPGEH) and the ProHealth study. Participants were sequenced by the Regeneron Genetics Center using the Illumina NovaSeq 6000 platform, and sample preparation and quality control were performed using a high-throughput, fully-automated system [PMID: 33087929]. Reads were aligned to the GRCh38 reference genome, and variants were called using WeCall [PMID: 33087929]. Participants with sex discordance, 20x coverage at less than 80% of targeted sites, and/or contamination greater than 5% were excluded. After quality control, we retained n = 6,247 (3,111 cases, 3,136 controls) individuals for downstream analyses. Among participants selected for this WES study, n = 5,432 (2,299 cases; 3,133 controls) consented to deposition of data to the National Institutes of Health (NIH).Further quality control was applied to filter low quality variants. Genotype calls with low depth of coverage (DP) were updated to missing (DP < 7 for SNPs and DP < 10 for indels), after which sites with low allele balance (AB) - variants without at least one sample having AB ≥ 15% for SNPs or AB ≥ 20% for indels - were removed. Lastly, variants with missingness > 10% and Hardy-Weinberg equilibrium p-value < 10-15 were excluded. Further description of quality control and downstream single-variant and gene-based analyses is available in Cavazos et al, 2022 [medRxiv].

  Study phs002809

• Integrative Molecular Characterization of Breast Cancer

  Version 1: We have performed integrative analyses of breast cancer tumors, including whole exome sequencing (WES) of tumor and normal pairs, whole transcriptome sequencing, and single-cell RNA sequencing (scRNA-seq) or single-nucleus RNA sequencing (snRNA-seq), to determine molecular correlates of response to novel and immune therapies. We have focused on dissecting the role of anticancer immunity in response to these therapies and understanding biological mechanisms underlying therapeutic resistance. The goal of this work is to advance a precision medicine approach to breast cancer treatment by identifying molecular biomarkers to improve therapy selection and novel therapeutic targets to overcome resistance. Version 2: We performed bulk whole exome sequencing (WES) of fresh frozen tissue from primary hormone receptor-positive breast cancer. Additionally, where available, we performed bulk whole transcriptome sequencing for the same individuals (tumor only). Additionally, we performed single cell sequencing on fresh frozen tissue from primary hormone receptor-positive breast cancer.

  Study phs002419

• Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma

  Follicular lymphoma (FL) is an incurable B-cell malignancy characterized by the t(14;18) and mutations in one or more components of the epigenome. Whilst frequent gene mutations in signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlap with the closely-related diffuse large B cell lymphoma (DLBCL). A combination of discovery exome and extended targeted sequencing revealed recurrent somatic mutations in RRAGC uniquely enriched in FL patients (17%). More than half of the mutations preferentially co-occurred with ATP6V1B2 and ATP6AP1 mutations, components of the vacuolar H+-adenosine triphosphate ATPase (v-ATPase) known to be necessary for amino acid-dependent mTORC1 activation. RagC mutants increased raptor binding whilst rendering mTORC1 signaling resistant to amino acid deprivation through nucleotide-independent mechanisms. Collectively, the activating nature of the RRAGC mutations, their existence within the dominant clone and stability during disease progression supports their potential as an excellent candidate to be therapeutically exploited.

  Study EGAS00001001190

• UNC Tumor Donation Program Set 2021

  The goal of this study is to study gene expression patterns in primary, metastatic tumors, and normal tissues.

  Study phs002429

• One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids

  Recent optimization of CRISPR/Cas9-mediated genome engineering has resulted in the development of base editors that can efficiently mediate C>T and A>G transitions. Combining these genome engineering tools with human adult stem cell (ASC)-derived organoid technology holds promise for disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived hepatocyte, endometrial and intestinal organoids. First, using conventional and evolved Cas9-variants, we show efficacy of both cytosine and adenine base editors and use them to model four hot-spot point mutations in CTNNB1 in hepatocyte organoids. Next, we apply C>T base editors in endometrial organoids to insert nonsense mutations in PTEN and demonstrate tumorigenicity even in the heterozygous state. Furthermore, we use cytosine base editors for simultaneous oncogene activation (PIK3CA) and tumor-suppressor inactivation (APC and TP53). To increase the flexibility of base editor multiplexing, we then combine SpCas9 and SaCas9 base editors for simultaneous C>T and A>G editing at individual target sites. Finally, we show the power of base editor multiplexing by modeling colorectal tumorigenesis in a single step by simultaneously transfecting sgRNA’s targeting four cancer genes. Seven clonal organoid lines and one bulk wild-type control sample were paired-end whole-genome sequenced using the Illumina Novaseq 6000 system. We sequenced four clonal intestinal organoid lines harbouring engineered TP53 and FBXW7 mutations as well as three lines targeted for oncogenic APC/TP53/PIK3CA/SMAD4 mutations. This WGS showed, as previously reported, a genome-wide increase in C>T mutations due to C>T base editor off-target activity, which is not enriched in predicted off-target regions based on the sgRNA sequences. Furthermore, we confirmed the absence of editing-induced driver mutations and lack of off-target mutational hotspots created by the genomic engineering.

  Study EGAS00001006886

• Autosomal recessive CD70 deficiency is associated with combined immunodeficiency and EBV viremia

  We describe four patients from two unrelated families of different ethnicities who had primary immunodeficiency predominantly manifesting as susceptibility to EBV-related diseases. We performed whole exome sequencing (P1 and P2 from family 1) or whole genome sequencing (P4 and both parents from family 2) in those two families and identified homozygous frameshift or in-frame deletions in CD70 in these patients which abolished either CD70 surface expression or binding to its counter structure CD27. Sanger sequencing identified the same homozygous CD70 mutation in P3, which is not included in the dbGaP submission. Autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of CD27 deficiency.

  Study phs001245

• Mannheim Liquid Biopsy Unit, Heidelberg University & DKFZ

  The dataset consists of sequenced cell free DNA (cfDNA) samples from colorectal cancer patients. The samples were sequenced on an Illumina MiSeq machine using a custom amplicon sequencing approach. These amplicons were designed to cover the most common mutation hotspots in colorectal cancer. The data include 138 cfDNA samples from 34 different patients. For each patient several samples are available derived from blood drawn at different time points during treatment. In addition the data include samples from 22 histology slides and 30 samples derived from HT29/HCT116 cell lines that were used as controls.

  Dataset EGAD00001004574

• Monotherapy_Breast_Cancer

  These samples are from locally advanced breast cancers that have been treated with epirubicin monotherapy before surgery. We will sequence some samples from patients with good response to the therapy and some with poor response to the therapy.

  Study EGAS00001000165

• Transcriptomic Profiles of Neoantigen-Reactive T Cells in Human Gastrointestinal Cancers

  This study explores the transcriptomic profiles of neoantigen-reactive tumor-infiltrating lymphocytes (TILs) from human bile duct and pancreatic cancer. The submitted data are bulk tumor RNA-Seq, tumor and germline whole-exome sequencing from 10 patients, and single cell RNA-Seq data from TIL of 5 of these patients.

  Study phs002765

• B Cell Receptor Study From Early Breast Cancer Tumour Samples

  B and T cells are key components of the adaptive immune system and play an important role in anti-cancer immunity. In this study, we performed an integrative analysis of the B cell and T cell repertoires across 25 serial breast tumour biopsies from 10 patients during neoadjuvant therapy.

  Study EGAS50000000241

• SCLC MeDIP

  Mimicry of neuronal features are emerging as malignant regulators of cancer growth and metastasis. Neuroendocrine (NE) cancers and small cell lung cancers (SCLC) in particular have been shown to share expression profiles marking various stages of neuronal differentiation. Here, methylation profile from SCLC patients' tumour and normal tissue has been investigated genome wise.

  Study EGAS50000000506

• Analysis_of_resistance_to_PLX4032

  We have collected material from a patient who had BrafV600E mutant melanoma that wastreated with PLX4032. We have germline DNA from the patient and DNA and RNA fromdistinct lesions before and after treatment with PLX4032. We would like to exome sequencethese samples to gain a snap shot of the mechanisms of resistance that are operative.

  Study EGAS00001000415

• The_Transcriptome_of_PLX4032_resistance

  We have collected material from a patient who had BrafV600E mutant melanoma that wastreated with PLX4032. We have germline DNA from the patient and DNA and RNA fromdistinct lesions before and after treatment with PLX4032. We have transcriptome sequenced these samples to obtain a snap shot of the mechanisms of resistance that are operative.

  Study EGAS00001000413

• A Comprehensive Catalogue of Somatic Mutations from a Human Cancer Genome

  We have carried out complete sequencing of the genome of the human male maligant melanoma cell line COLO-829 using the Illumina Genome Analyzer II. We generated a sequencing library with a median insert size of ~200 bp following random fragmentation and gel fractionation of the genomic DNA. We sequenced 75 bases from both ends of these templates to cover the COLO-829 genome to an average depth of more than 40x. We have carried out purity-filtering (PF) to remove mixed reads, where two or more different template molecules are close enough on the surface of the flow-cell to form a mixed or overlapping cluster. No other filtering of the data has been carried out prior to submission. We have also submitted sequence data for a lymphoblastoid control cell line COLO-829BL from the same individual.

  Study EGAS00000000052

• Surgery in combination with immune checkpoint therapy as an effective treatment for patients with metastatic cancer.

  Abstract Surgical removal of primary tumors was shown to reverse tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT)-containing treatments is not understood. Here, we report the first prospective, non-comparative clinical trial (N=104) using three different ICT-containing strategies plus cytoreductive or “debulking” surgery to remove the primary tumor-bearing kidney or a metastatic lesion as a treatment for patients (N=43) with metastatic clear cell renal cell carcinoma (mccRCC). For those patients (N=61) who were not candidates for cytoreductive surgery, a biopsy was obtained instead for correlative biological studies. Our data demonstrated that the combination of ICT with cytoreductive surgery was safe and feasible in patients with mccRCC. The 2-year overall survival was 84% with a median OS of 54.7 months for patients who received ICT containing regimens plus surgery. Immune-monitoring studies with co-detection by indexing (CODEX) identified distinct tumor spatial conformation of cellular subsets as a novel and improved predictor of response to ICT. Importantly, single-cell RNA-sequencing data demonstrated that surgical removal of the tumor increased antigen-presenting dendritic cell population with a concurrent reduction in KDM6B expressing immune-suppressive myeloid cells in the peripheral blood. Together, this study highlighted the feasibility of combining ICT with cytoreductive surgery in a metastatic setting and demonstrated potential enhancement of immune responses following ICT plus cytoreductive surgery in patients with metastatic disease.

  Study EGAS00001005667

• Multimodal plasma and urinary cell-free DNA profiling improves risk stratification in newly diagnosed prostate cancer

  Prostate cancer (PCa) is a heterogeneous disease, impeding early detection and risk stratification. Liquid biopsies (LBx) enable minimally invasive tumor profiling, but circulating tumor-derived DNA (ctDNA) detection remains difficult, particularly in early-stage PCa. We developed a multimodal LBx approach combining genomic and epigenomic cell-free DNA (cfDNA) features in plasma and urine from newly diagnosed PCa patients to improve early characterization of PCa and risk stratification of aggressive disease. Plasma and urine samples from 55 localized PCa (lPCa) patients, 18 advanced PCa (aPCa) patients, and 36 cancer-free controls were subjected to low-coverage whole-genome sequencing and methylated DNA immunoprecipitation sequencing to assess fragmentation, chromosomal instability, and methylation in cfDNA. This complementary approach yielded a 45% ctDNA detection rate in newly diagnosed PCa. Major differences were observed between aPCa and controls, reflecting increasing signals with tumor progression. Epigenomic cfDNA features differentiated lPCa from aPCa, and ctDNA was detected in 46% of PCa patients with prostate-specific antigen <10 ng/ml, suggesting potential for risk stratification. This study highlights the value of multimodal LBx approaches for early characterization of primary PCa and identification of aggressive disease at initial diagnosis. Integration into clinical workflows could complement diagnostics and support personalized decision-making tailored to patients’ PCa risk profiles. 

  Study EGAS00001008195

• Tobacco exposure and somatic mutations in normal human bronchial epithelium

  That tobacco smoking causes lung cancer is well-established, but we lack quantitative understanding of its effects on genomes of normal bronchial epithelium. We sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking is the major influence on mutation burden, adding 1000-10,000+ mutations/cell, massively increasing both between-subject and within-subject variance, and generating several distinct signatures of substitutions and indels. A population of cells in subjects with smoking history had mutation burdens equivalent to that expected for never-smokers: these cells lacked tobacco-specific mutational signatures, were four-fold more frequent in ex-smokers than current smokers, and had significantly longer telomeres than their more mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged never-smokers. In current smokers, ≥25% of cells carried driver mutations and 0-6% cells had 2 or even 3 drivers. Thus, tobacco smoking increases mutation burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.

  Dataset EGAD00001005193

• APOBEC mutagenesis is a common process in normal human small intestine

  The single base substitution mutational signatures SBS2 and SBS13, likely caused by APOBEC cytosine deaminases, are common in many human cancer types. However, the stimulus activating APOBEC mutagenesis is unknown and understanding of when it occurs in the progression from normal to cancer cell is limited. Here, as part of a wider survey of human tissues, we whole genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals. SBS2/13 mutations were present in 17% normal small intestine crypts and were likely due to APOBEC3A activity. Localised clusters of SBS2/13 mutations (kataegis) were also commonly found. APOBEC mutation burdens were variable between individuals and between crypts from the same individual. Crypts with SBS2/13 often had immediate crypt neighbours without SBS2/13, suggesting that the underlying cause of SBS2/13 is cell-intrinsic rather than a widely distributed microenvironmental exposure, or needs to be permitted by cell-intrinsic conditions. APOBEC mutagenesis occurred throughout the human lifespan, including in young children, and was episodic with a small number of episodes occurring during the life history of a single cell. The results indicate that APOBEC mutagenesis is more common in the small intestine epithelium than in many other cell types, and is an episodic process in vivo initiated or permitted by cell intrinsic factors.

  Dataset EGAD00001008764

• Molecular Genetics of Heterotaxy and Related Congenital Heart Defects

  Heterotaxy syndrome is a congenital anomaly syndrome accompanied by thoracic and abdominal situs abnormalities. The study cohort comprises of individuals with heterotaxy or related congenital heart disease (CHD) who have undergone exome sequencing. The purpose of the study is to elucidate the molecular genetics of the disorder as well as contribute to knowledge about the biology of normal and abnormal development of left-right anatomic asymmetry. These results will further help delineate genotype-phenotype associations and provide important information on the causes, management, and prognosis of heterotaxy syndrome.

  Study phs001814

• National Cancer Institute (NCI) Genome-Wide Association Study (GWAS) of Renal Cell Carcinoma in African Americans

  The NCI GWAS of renal cell carcinoma (RCC) in African Americans was undertaken to provide insight into genetic loci affecting susceptibility to this malignancy in a racial group known to be at elevated risk. We genotyped 1,136,723 single-nucleotide polymorphisms (SNPs) among 255 cases and 375 controls of African ancestry from the NCI Kidney Cancer Study, and further investigated 16 SNPs in a replication set consisting of 140 cases and 543 controls from a case-control study conducted at the University of Texas MD Anderson Cancer Center. The variant rs10771279 located on 12p11, 77kb from a European-ancestry RCC risk marker, was associated with RCC risk in the GWAS (P=1.2 x 10-7) but did not replicate (P=0.99). The variant 7105934 on 11q13.3, previously associated with RCC in a GWAS using European-ancestry samples, was associated with risk in both studies [meta-analysis odds ratio (OR)=0.76, 95% confidence interval (CI)=0.64-0.91; P=0.0022]. The frequency of this allele was higher than that observed in the European-ancestry GWAS (0.56 and 0.07 respectively among controls). The rs7105934 association was stronger for clear cell RCC (ccRCC: OR=0.56; P=7.4 x 10-7) and absent for cases of other or unknown histology (OR=1.02; P=0.86). In conclusion, this study provides evidence that rs7105934 is a susceptibility locus for RCC, and clear-cell RCC in particular, among African Americans.

  Study phs000863

• HiChIP data and analysis in OCI-AML3

  Data and analysis of HiChIP assay of shZNF143 and shControl in OCI-AML3. CTCF was the ChIP antibody. Data files are paired-end reads in FASTQ format from the Illumina NovaSeq 6000 sequencer. Analysis files are paired-end bed files produced by FitHiChIP.

  Dataset EGAD50000001376

• Therapy-related myeloid neoplasms and HSPCs from the International-Berlin-Frankfurt-Münster (I-BFM) Study group

  Dataset contains WGS sequencing data from bulk sorted therapy-related myeloid neoplasms (t-MN) and reference cells (MSCs/B cells/T cells). In addition, from 4 patients, also WGS data from single hematopoietic stem and progenitor cells, obtained from samples of t-MN diagnosis, are included. These are either clonally expanded before WGS, or DNA was directly amplified via the primary template-directed amplification (PTA) protocol (mentioned in the sample name).

  Dataset EGAD00001011256

• Acquired Copy Number Alterations in Adult Acute Myeloid Leukemia Genomes

  We performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult patients with de novo AML using the Affymetrix Genome-Wide Human SNP array 6.0 containing 1.85 million features. Acquired copy number alterations (CNA) were confirmed using an independent, higher resolution, custom array comparative genomic hybridization platform. A total of 201 somatic CNA were found in the 86 AML genomes (mean 2.34 CNA/genome), with FAB M6 and M7 AML genomes containing the most changes (10-29 CNA/genome). Twenty-four percent of AML patients with normal cytogenetics had CNA, while 40% of patients with an abnormal karyotype had additional CNA detected by SNP array, and several regions contained CNA in multiple AML genomes. The mRNA expression levels of 57 genes were significantly altered in 27 of 50 recurrent CNA regions <5 megabases in size. Array data are available online at http://www.ncbi.nlm.nih.gov/geo/ as GEO accession #GSE10358. A total of 8 uniparental disomy (UPD) segments were identified in the 86 genomes and 6/8 UPD regions occurred in samples with a normal karyotype. Collectively, 40% of AML genomes contained alterations not found with cytogenetics, and 96% of these regions contained known or novel AML associated genes. 43/86 AML genomes had no CNA or UPD at this level of resolution. The number of CNA per genome was not associated with overall survival, independent of cytogenetic classification. In this study of 86 adult AML genomes, subcytogenetic CNAs or UPD did not add prognostic information to standard cytogenetics. However, arrays identified many somatically mutated oncogenes and tumor suppressor genes, and also genes not previously implicated in AML that may be relevant for pathogenesis. AML CNA segments from 86 adult AML patients are available through dbVar at ftp://ftp.ncbi.nlm.nih.gov/pub/dbVar/data/Homo_sapiens/nstd11_Walter_et_al_2009.

  Study phs000201

• A Genome-Wide Association Comparative Analysis of Response of AF Patients to Rate Control Therapy; A Collaboration between the NIH Pharmacogenomics Research Network and the RIKEN Yokohama Institute Center for Genomic Medicine

  The goal of this study was to identify genetic predictors of response to rate control therapy in patients with AF. We conducted a genome-wide association study (GWAS) focusing on subjects with a history of atrial fibrillation. Rate control therapy for AF uses a range of drugs (beta-adrenergic receptor blockers, calcium channel blockers, and digitalis) to depress conduction through the AV node, thereby preventing rapid rates and minimizing symptoms. In large groups of patients, such as the Vanderbilt AF Registry (a clinical and genetic repository with over 1200 patients with ECG-confirmed AF) from which these study subjects were drawn, approximately 5% display failure of aggressive AV nodal-blocking therapy to control ventricular rate. In these patients, interruption of the AV node by ablation and pacemaker implantation are necessary for adequate rate control. Study cases were individuals who underwent AV node ablation and pacemaker implantation after combined therapy with 3 AV nodal-blocking agents was ineffective in rate control. Controls for this study were individuals who met standardized rate-control efficacy criteria (as described in AFFIRM study, Wyse et al, NEJM 2002; PMID: 12466506) for optimal rate control with 2 or fewer AV nodal-blocking agents. Two additional groups were genotyped by RIKEN: An additional group of patients with AF as well as subjects undergoing cardiac surgery in whom AF did not occur post-operatively. All study participants were recruited and treated/evaluated at Vanderbilt University Medical Center. This study was conducted by the Pharmacogenomics of Arrhythmia Therapy subgroup of the Pharmacogenetics Research Network, a nationwide collaboration of scientists studying the genetic contributions to drug response variability. Genotyping was performed by the RIKEN research institute in Japan using the Illumina 610 Quad Beadchip platform.

  Study phs000439

• Integrated Analysis of Multimodal Single-Cell Data

  The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce 'weighted nearest neighbor' analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity. All CITE-seq and ECCITE-seq raw matrices are available in GEO database under the accession number GEO: GSE164378.

  Study phs002315

• RNAseq of breast cancer bone metastases PDX resistant of responder to IACS-010759 treatment

  Fastq files from RNAseq of breast cancer bone metastases PDX after treatment with IACS-010759. Five PDX are resistants to treatment and 6 are responders.

  Dataset EGAD00001009072

• Highlighted samples from the BCH CRDC

  These exomes are from some of the patients and family members detailed in our forthcoming publication, Children’s Rare Disease Cohorts: an integrative research and clinical genomics initiative. While this paper details an institutional collection of exomes, the samples here were specifically highlighted as having significant findings.

  Study EGAS00001004436

• Whole exome sequencing of 76 individuals with familial atrial fibrillation

  We investigated genetic background of familial and early onset atrial fibrillation (AF) with the aim of identify genes involved in atrial fibrillation pathology and are highly predisposing risk factors. We performed whole exome sequencing on 24 families where three or more family members suffered from AF.

  Study EGAS00001003207

• Separation of chronic myeloid leukemia stem cells from normal hematopoietic stem cells at single-cell resolution

  We provide whole exome DNA sequening data in fastq format for 23 clinical samples of chronic myeloid leukemia stem cells (CML-SC) plus two buccal swipes derived normal samples. CML samples are comprised of 4 to 8 replicates from two patients, at diagnosis and after treatment. Single CML stem cells before treatment and single non-transformed hematopoietic stem cells (HSC) at remission were selected from bone marrow samples by FACS, according to newly identified genetic markers CD33+CD26+ at diagnosis and CD33+CD26-/CD33-CD26- at remission. WES libraries of colony forming assays derived CML-SC and HSC populations were prepared using Agilent SureSelect Human All Exon V6 kit and sequenced running 150 cycles (2x 75bp paired-end) on an Illumina NextSeq 500 platform.

  Dataset EGAD00001009847

• Genomic Analysis of Paired Endometrial Cancer Primaries and Metastases

  Formation of metastases is the major cause of cancer related deaths. Recent studies have sequenced primary endometrial carcinomas yielding data for a single entity in the progression from the birth of a progenitor tumor cell to metastatic disease. However, the progression of these tumors to metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed TCGA-data, identifying novel recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor NRIP1 in 12% of patients. We found that likely driver events tended to be shared by primary and metastatic tissue-samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses in cases with multiple metastases indicated these metastases typically arose from one lineage of the primary tumor. These data indicate extensive genetic heterogeneity within endometrial cancers and relative homogeneity across metastatic sites.

  Study phs001127

• Resolving the immune landscape of human prostate at a single cell level in health and cancer

  The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. We used single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate and identified a previously unappreciated subset of tumour-enriched androgen receptor-negative luminal epithelial cells, with increased expression of cancer-associated genes. We also found a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception was a unique, prostate-specific, zinc transporter-expressing macrophage population (MAC-MT), that contributed to tissue zinc accumulation in homeostasis, but showed enhanced inflammatory gene expression in tumours, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies was associated with improved disease-free survival, suggesting beneficial anti-tumour functions.

  Study EGAS00001005787

• Oral Microbiome in Esophageal Adenocarcinoma

  The purpose of our study was to assess the influence of oral microbiota on the development of esophageal cancer. Our preliminary case-control studies reported a global alteration of foregut microbiome in esophageal adenocarcinoma with the strongest changes found in the oral microbiome. We hypothesise that commensal oral bacteria are capable of activating or degrading carcinogens in cigarette smoke and therefore may contribute to esophageal carcinogenesis. We conducted a prospective study nested in two large US cohorts, to determine whether oral microbiota are associated with subsequent esophageal adenocarcinoma.

  Study phs001527

• SUM-seq data for spontaneous differentiation of iPSCs upon perturbation of GATA2, NR4A2 or SOX17

  We combined SUM-seq with arrayed CRISPR screening, modulating the expression of key lineage transcription factors (TFs) (GATA2 - mesoderm, SOX17 - endoderm, and NR4A2 - neuroectoderm) in hiPSCs via CRISPR interference (CRISPRi) or activation (CRISPRa) over a time course of spontaneous differentiation (days cultured in vitro: 0, 4, 12, and 18). This totalled to 54 samples (4 day/time points x 3 target TFs x 2-3 gRNAs per target x CRISPRi/a). Single-cell chromatin accessibility and gene expression data is provided as demultiplexed fastq files.

  Dataset EGAD50000001205

• Chracterising cellur pathways underlying CD3/CD28 activation of human CD4+ cells

  We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Isolated memory and naïve T cells were activated using anti-CD3, anti-CD28 or both in combination. As a control we cultured cells in the same conditions but without the stimuli. We carried Chipmentation using the H3K27ac antibody on 200,000 cross-linked cells. 1) 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 please see http://www.sanger.ac.uk/datasharing/ .

  Dataset EGAD00001006611

• Resolution and methylation patterns of supernumerary marker chromosomes

  Herein we study the structure of ring and marker chromosomes in 10 carriers. The aim is to gain understanding of the formation and function of ring and marker chromosomes.

  Study EGAS50000001466

• Myocardial Infarction Genetics Exome Sequencing Consortium: German Heart Center in Munich

  The Munich-MI study is a case-control cohort study recruited at the German Heart Center in Munich, Germany. It is focused on understanding the genetic contributors to early myocardial-infarction (MI) in the German population. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Illumina's ICE Capture reagent and sequencing was performed on an Illumina HiSeq 2000 or 2500.

  Study phs000916

• OTOF mutation analysis with massively parallel DNA sequencing in 2,265 Japanese sensorineural hearing loss patients.

  The OTOF gene, encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS) to reveal the frequency and clinical characteristics of OTOF-related hearing loss in a large hearing loss population.

  Study JGAS000166

• Breast Cancer Follow Up Series

  This study's purpose is to use data generated in whole genome and exome Breast Cancer sequencing to target specific areas in multiple other Breast Cancer samples. These areas will then be subjected to PCR in multiple cases, tagged and then pool the resultant amplicons. These amplicons will then be sequenced on the Illumina GAII. This is hoped to show the prevalence of previous findings in multiple individuals in a high throughput method.

  Study EGAS00001000002

• glioblastoma single cell RNAseq

  Understanding the cellular origin and differentiation status of glioblastoma is critical to resolve the etiology of the disease. we profile 18 patient glioblastomas by single cell RNA sequencing (scRNAseq). From this, we uncovered two principal cell-of-origin relations. Each lineage displays unique directional differentiation trajectories and transcriptional cores from the naïve cell populations. Thus, glioblastoma is defined by robust cell lineage features which may provide insights into the cell origin of the diseases.

  Study EGAS00001006236

• Differential Wnt/β-Catenin Signaling Activities Shape Distinct Tumor Cell Phenotypes

  By profiling patient-derived hepatoblastoma organoids via single-cell transcriptomics and chromatin dynamics, we identify subtype-specific transcriptional and epigenetic profiles. Using CUT&RUN, we show that β-catenin engages distinct genomic regions, which is dictated by differential association with TCF/LEF family transcription factors. TCF7L2 binds to a motif, distinct from the classical Wnt consensus sequence, which is found in the promoter of hepatic target genes.

  Study EGAS50000001229

• Genomic Profiling of Peripheral T-cell Lymphoma

  Peripheral T-cell lymphomas (PTCLs) are malignant and highly aggressive hematologic tumors arising from mature post-thymic T cells. The diagnosis of PTCL includes diverse lymphoma subgroups, altogether accounting for about 15% of all non-Hodgkin lymphomas. Despite recent advances in uncovering the mutational landscape of PTCLs, the prognoses of most PTCLs remain poor. To overcome the limits of exome sequencing and identify new genomic abnormalities in PTCL, we performed RNAseq and whole genome sequencing. From our analyses, we identified a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7). These genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support an oncogenic role for VAV1 signaling in the pathogenesis of PTCL (Abate et al., 2017). Recently, we have also identified a novel chimeric oncogene, FYN-TRAF3IP2, in the RNA-seq and whole genome sequencing analyses. FYN-TRAF3IP2 leads to aberrant NF-κβ activity downstream of T-cell receptor signaling and induces NF-κβ-driven T-cell transformation when expressed in hematopoietic progenitors in mice. This novel gene fusion supports the oncogenic driver role of NF-κβ signaling in the pathogenesis of PTCL (Kim et al., in review).

  Study phs001962

• MutWP5: CRUK Mutographs of Cancer: Lung: PD37920 (Targeted) (2021-02-02)

  Sequencing of LCM-derived microbiopsies from explanted lung from COPD patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs. . This dataset contains all the data available for this study on 2021-02-02.

  Dataset EGAD00001006929

• A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

  Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

  Study EGAS00001005493

• deep-learning-powered tissue deconvolution for cfDNA

  Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.

  Study EGAS00001007213

• International Cancer Proteogenomics Consortium (ICPC): Proteogenomics of East-Asian Breast Cancer

  The incidence of invasive breast cancer is rapidly increasing in East Asia, enriching in younger patients and luminal disease. We presented a deep proteogenomic landscape of a prospectively enrolled early-stage cohort in Taiwan to uncover the etiology, age-related subtype and oncogenic vulnerabilities underlying the heterogeneous disease. Multilayer proteogenomic architecture revealed distinct endogenous and environmental carcinogen-associated mutagenesis, linking APOBEC (apolipoprotein-B mRNA editing enzyme, catalytic polypeptide-like) cytidine deaminase and DBAC (dibenz[a,j] acridine) signatures to significantly elevated hormone biosynthesis and chemical carcinogenesis in younger patients, and identifying a novel subset of high mutation burden and immune escape potentially beneficial from combined epigenetic therapy and immunotherapy. A proteomics-informed classification resolves luminal heterogeneity, defines high-risk recurrent luminal disease and nominates biomarkers and actionable druggable pathways. Furthermore, proteogenomics profile distinguished a young luminal population susceptible to exogenous carcinogen and having DNA repair deficiency. This study illuminates the age-related molecular subtypes and oncogenic vulnerabilities, providing a proteogenomics-transformative guide for patient stratification and precision therapeutics beyond clinical staging.

  Study phs003150

• European BestAgeing Study on microRNA candidates for cardiovascular disease

  Background: Circulating miRNAs have emerged as promising biomarker candidates due to their stability and their role in regulating key pathological pathways in cardiovascular disease (CVD). Yet, large-scale, multicenter studies examining their diagnostic and prognostic potential are scarce. This study evaluates the potential of miRNA expression profiles to inform disease classification and risk stratification across major CVD phenotypes, including acute coronary syndrome (ACS), chronic coronary artery disease (CAD), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM), in a large, multicenter European cohort. Methods: We assessed genome-wide miRNA expression profiles in a total of 1,209 cardiovascular patients and 848 controls in a uniform, standardized fashion, which renders this study one of the largest prospective miRNA studies. To focus on only the most biologically plausible miRNAs for clinical translation, we mined all original studies of miRNA candidates in CVD and performed differential miRNA expression and enrichment analysis. We then trained disease-specific binary classification models to evaluate the diagnostic potential of miRNA signatures. Finally, we evaluated prognosis and disease severity based on distinct miRNA levels. Results: 634 original abstracts were identified, detailing 166 ACS, 181 CAD, 56 DCM, and 182 ICM miRNAs. Without further optimization, the signatures of a priori miRNAs already yielded very good diagnostic performance with ROC AUC of 0.83 – 0.95. There was an improvement when considering additional miRNAs in a discovery setting. Interestingly, in ACS, CAD and DCM we observed a significantly worse prognosis in probands with higher scores in the miRNA signatures, indicating additional prognostic information. Conclusions: The European BestAgeing miRNA study reveals emerging associations of several miRNA signatures with cardiovascular disease discrimination and prognostication, providing a foundation for future external validation and potential clinical translation of this class of markers.

  Study EGAS00001008346

• High Resolution Analysis of Spatial Interactions of Hundreds of Promoters in HeLa Cells

  In this study we developed a new hybridisation-based promoter Capture-C protocol that makes use of biotinylated dsDNA probes and allows high-resolution promoter interactome description. Experiments aimed to describe spatial interactions of set of 861 promoters were performed in HeLa cells. We have found that enrichment efficiency and quality of final libraries in our study is on a par with established promoter Capture-C protocols. Meanwhile, our version of the probe preparation protocol is reasonably simple and makes Capture-C experiments more affordable and flexible.

  Study phs002014

• SF11949 snATAC Seq IDH1 mutant oligodendroglioma Male

  IDH1 mutant oligodendroglioma male, 40. Single Nuclei ATAC seq data from low grade human glioma sample. NovaSeq6000 was used for ATAC seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005398

• SF12017 snATAC Seq IDH1 Mutant GBM 55, Male

  IDH1 mutant GBM 55, Male. Single Nuclei ATAC seq data from high grade human glioma samples. NovaSeq6000 was used for ATAC seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005405

• SF11215 snATAC Seq GBM

  High grade glioma sample, Gender Male Age 46. Single Nuclei ATAC seq data from high grade human glioma samples. NovaSeq6000 was used for ATAC seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005407

• SF11331 snATAC Seq Primary GBM Male

  SF11331 Primary GBM Male,55 Single Nuclei ATAC seq data from high grade human glioma sample. NovaSeq6000 was used for ATAC seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005408

• SF11612 scRNA-Seq Recurrent oligodendroglioma

  Single Cell RNA seq from Recurrent oligodendroglioma sample. Gender Male Age 67. NovaSeq6000 was used for RNA seq. The files uploaded are bam files created with grch38 reference through Cellranger count (10xGenomics.)

  Dataset EGAD00001005411

• SF11612 snATAC Seq Recurrent oligodendroglioma

  SF11612 Recurrent oligodendroglioma. Gender Male Age 67. Single Nuclei ATAC seq data from low grade human glioma samples. NovaSeq6000 was used for ATAC seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005413

• SF9259S snRNA-Seq Primary GBM

  Single Nuceli Primary GBM 73 Male. Single Nuclei RNA seq from high grade primary glioma sample. NovaSeq6000 was used for RNA seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005428

• ESGI - Whole Genome Sequencing of samples from the Croatian isolated populations (2017-11-22)

  Whole genome sequencing of sampels from isolated populations from Croatia. The samples are sequenced using the Illumina HiSeq X Ten system. This dataset contains all the data available for this study on 2017-11-22.

  Dataset EGAD00001003812

• A practical guide for mutational signature analysis in hematological malignancies

  Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data.

  Dataset EGAD00001005028

• The Genetic Landscape of Mutations in Burkitt Lymphoma

  Burkitt lymphoma (BL) is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. We sequenced exomes of 59 BL tumors, 14 of which had paired normal tissue. Our work elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a novel tumor suppressor gene.

  Study phs000562

• Single cell transcriptomic profiles of advanced melanoma patients treated with checkpoint inhibitor immunotherapy

  Little is known about the resistant clones within the tumour ecosystem treated with immunotherapy. This work provides a comprehensive and integrative analysis of each individual non-responding melanoma patients, including clinical features integrated with single cell analysis, which is critical to understand features of resistance in order to improve cancer patients’ outcomes.

  Study EGAS50000000339

• Neuroblastoma patient WGS data

  Paired tumor and normal WGS of primary neuroblastomas. This is an update of the „Berlin Neuroblastoma Dataset” (EGAS00001004022). This data was used for the analysis of circular RNA expression and regulation in neuroblastoma.

  Dataset EGAD00001008123

• Clinical and biomarker dataset

  Clinical & biomarker data from IMagyn050: treatment arm, treatment approach, outcome of surgery, ECOG PS, PD-L1 status, race, age, disease stage, progression free survival (investigator assessed), overall survival, histology, tumor mutation burden and status, genomic loss of heterozygosity, microsatellite status, BRCA1/2 mutation status, tissue of origin. Mutation status based on FoundationOne NGS for the following genes is also being provided: TP53, BRCA1, CCNE1, MYC, NF1, PIK3CA, RAD21, TERC, PRKCI, KRAS, RB1, BRCA2, ARID1A, AKT2, PTEN, KDM5A, NOTCH3, FGF12, ERBB2, CDK12, EMSY, WHSC1L1, BCL2L1, CDKN2A, GNAS, ARFRP1, ZNF217, SOX2, CCND2, FGF6, FGF23, LYN, MUTYH, AURKA, FGFR1, MCL1, MLL2, MYCL1, ZNF703, BRAF, MAP2K4, CREBBP, TSC2

  Dataset EGAD00001009797

• SOFT study - sequencing premenopausal breast cancer (2017-11-22)

  Our project will examine the role of PIK3CA mutations and their sensitivity to endocrine therapies and its role, with the addition of complete ovarian suppression. We plan to test our hypotheses using tumour samples collected from patients enrolled in the SOFT/IBCSG24-02 clinical study (Suppression of Ovarian Function Trial - (NCT00066690). SOFT is a phase III trial that randomised 3066 premenopausal women to evaluate if adding ovarian suppression to adjuvant endocrine therapy will improve clinical outcomes. This dataset contains all the data available for this study on 2017-11-22.

  Dataset EGAD00001003811

• Stand Up To Cancer East Coast Prostate Cancer Research Group

  Most prostate cancer deaths are caused by metastatic, castration resistant disease (mCRPC). To develop a precision medicine framework for mCRPC, we established a multi-institutional, international clinical sequencing infrastructure to enroll and carry out prospective whole exome and transcriptome sequencing of tumors from a cohort of mCRPC patients. We obtained high quality DNA and RNA sequence data from 150 bone or soft tissue biopsies. Central pathology revealed high-grade adenocarcinoma with only four cases (3.6%) showing neuroendocrine differentiation. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40-60% of cases), with TP53 and AR alterations being the most enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B (fusions and mutations); R-spondin, BRAF and RAF1 (fusions); APC (inactivating mutations); delta-catenin (missense mutations); and ZBTB16/PLZF (homozygous deletions). Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers, with 56% of these being exclusively somatic. Putative driver gene alterations were identified in nearly all patients, and over half also harbored driver gene fusions, homozygous deletions and/or amplifications. Moreover, 89% of patients harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. Overall, integrative clinical sequencing analysis can be safely and efficiently performed in mCRPC, yields findings that may be actionable for enrolling patients in clinical trials of targeted therapies, and may inform the basis of individual clinical responses.

  Study phs000915

• Whole Genome Profiling to Detect Schizophrenia Methylation Markers

  Schizophrenia (SCZ) is a devastating psychiatric disorder. The aim of this study was to detect DNA methylation (5meC) profiles in whole blood associated with SCZ. The sample consisted of schizophrenia cases and controls selected from national population registers in Sweden. We employed MBD protein-based enrichment of the methylated DNA fraction, followed by single end sequencing (50 bp reads) on the SOLiD platform. To improve methylome-wide coverage we used an existing protocol variant, which increases the relative number of fragments from CpG poor regions. To analyze the data, we used an analysis pipeline described elsewhere7, that was designed specifically for MBD-seq and included alignment, quality control (QC) of reads and samples, coverage calculations for the 26,752,702 autosomal CpGs in the reference genome using a non-parametric estimate of the fragment size distribution, an in silico experiment to identify CpGs in loci with alignment problems, a 2-stage adaptive algorithm to combine data from correlated adjacent CpG sites in "blocks", principal component analysis (PCA), association testing, bioinformatics annotation and network analysis. After QC, 1459 subjects with on average 32.4 million high quality reads remained. Association testing was performed on 4.3 million high quality blocks after regressing out possible assay related technical artifacts, sex/age, and unmeasured confounders through the PCA components.

  Study phs000608

• An RCOR1 loss-associated gene expression signature identifies a prognostically significant DLBCL subgroup

  Effective treatment of diffuse large B cell lymphoma (DLBCL) is plagued by heterogeneous responses to standard therapy, and molecular mechanisms underlying unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148 genomes with 91 matching transcriptomes in an R-CHOP-treated DLBCL cohort to uncover molecular subgroups linked to treatment failure. Systematic integration of high-resolution genotyping arrays and RNA-seq data revealed novel deletions in RCOR1 to be associated with unfavorable progression free survival (P = 0.001). Integration of expression data from the clinical samples with data from RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss-associated gene signature comprising of 233 genes. This signature identified a subgroup of patients with unfavorable overall survival (OS) (P = 0.023). The prognostic significance of the 233-gene signature for OS was reproduced in an independent cohort comprising of 195 R- CHOP treated patients (P = 0.039). Additionally, we discovered that within the IPI low risk group, the gene signature provides additional prognostic value that was independent of the cell-of-origin phenotype. Taken together, we present a novel and reproducible molecular subgroup of DLBCL, impacting risk-stratification of R- CHOP treated DLBCL patients and revealing a new avenue for therapeutic intervention strategies.

  Study EGAS00001001000

• ALK_inhibitors_in_the_context_of_ALK_dependent_cancer_cell_lines

  Anaplastic lymphoma kinase (ALK) has recently been found to be a critical cancer gene in cases of lung cancer, neuroblastomas and lymphomas. ALK inhibitors have recently shown significant activity in lung cancer patients with tumours that harbour the EML4-ALK gene rearrangement, but already drug-resistance is emerging. We have taken a lung cancer cell line H3122 (with the EML4-ALK rearrangement) and generated clones resistant to a small molecule inhibitor of ALK by serial exposure to the drug over 8 weeks. We now wish to characterise at the exome level whether the acquisiton of resistance has been accompanied by the development of new mutations that we can take forward for further study as the potential mechansims underlying the resistance. We therefore propose to exome sequence the parental NCI-H3122 cell line as well as drug-resistant clones.

  Study EGAS00001000082

• Spatiotemporal immune atlas of the first clinical-grade gene-edited pig-to-human kidney xenotransplant

  Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

  Study EGAS50000000244

• Patient-derived tumor organoids for personalized medicine in a rare case of hepatocellular carcinoma with neuroendocrine differentiation.

  We report the case of a 74-year-old man with a very rare subtype of hepatocellular carcinoma with neuroendocrine differentiation (HCC-NED). The patient presented with two independent tumors, a gastrointestinal stromal tumor in the stomach and a hepatocellular carcinoma in the liver. Both tumors were surgically removed in curative intent. Histopathological work-up of the liver tumor revealed poorly differentiated hepatocellular carcinoma (Edmondson-Steiner grade IV) with diffuse expression of neuroendocrine markers synaptophysin (SYP) and chromogranin (CHGA). Three months after resection, multifocal recurrence of the HCC with neuroendocrine differentiation (HCC-NED) was observed. In the meantime, tumor organoids have been generated from the resected HCC-NED and extensively characterized. Sensitivity to a number of drugs approved for the treatment of HCC or neuroendocrine carcinomas was tested in vitro. Based on their in vitro efficacy, etoposide and carboplatin were used as first line palliative combination treatment. Because genomic analysis revealed a NTRK1-mutation (kinase domain) and tumor organoids were sensitive to entrectinib, a pan-TRK inhibitor, the patient received entrectinib as second line therapy. After only two weeks, treatment had to be discontinued due to deterioration of the patient’s general condition. In conclusion, we demonstrate for the first time that preclinical drug testing using organoids is feasible in selected HCC cases.

  Study EGAS00001005887

• Summary Statistics GWAS SSNS

  Column 1 rsid: SNP identifier;Column 2 chromosome: name of chromosome on which the SNP is located;Column 3: position: base pair position on the chromosome;Column 4 minor_test_allele: the base that constitutes the minor allele;Column 5 major_allele: the base that constitutes the major allele;Column 6 maf: the frequency of the minor allele, indicated as a fraction of 1;Column 7 allele_freq_cases: the minor allele frequency in cases;Column 8 allele_freq_controls: the minor allele frequency in controls;Column 9 regression_pvalue: the p-value for the difference in allele frequency between cases and controls;Column 10 odds_ratio: the odds ratio, as calculated using logistic regression under an additive model with adjustment for the first ten principal components of ancestry

  Dataset EGAD00010002316

• COMPARE study: participants typed during UK Biobank version 2 array development phase

  The COMPARE study enrolled 29,066 British blood between donors between February 2016 and March 2017, the study aim is to find the optimum technology for haemoglobin screening (ISRCTN 90871183). All participants were at the time of recruitment active blood donors. The 4,796 participants in this dataset have consented to join the NIHR BioResource. Genotyping data was produced using the Thermo Fisher Scientific Axiom Genotyping platform. The UK Biobank version 2 array design was used, content on this array has been added to allow for accurate DNA based identification of human blood group antigens.

  Dataset EGAD00001005023

• Summary Statistics GWAS SSNS

  Column 1 “rsid”: SNP identifier Column 2 “chromosome”: name of chromosome on which the SNP is located Column 3: “position”: base pair position on the chromosome Column 4 “minor_test_allele”: the base that constitutes the minor allele Column 5 “major_allele”: the base that constitutes the major allele Column 6 “maf”: the frequency of the minor allele, indicated as a fraction of 1 Column 7 “allele_freq_cases”: the minor allele frequency in cases Column 8 “allele_freq_controls”: the minor allele frequency in controls Column 9 “regression_pvalue”: the p-value for the difference in allele frequency between cases and controls Column 10 “odds_ratio”: the odds ratio, as calculated using logistic regression under an additive model with adjustment for the first ten principal components of ancestry

  Dataset EGAD00001008782

• Repotrectinib in NTRK fusion–positive advanced solid tumors: a phase 1/2 trial

  Early-generation TRK tyrosine kinase inhibitors (TKIs) approved for treating NTRK fusion–positive (NTRK+) solid tumors provide clinical benefit; however, resistance emerges. Repotrectinib is a next-generation ROS1/TRK TKI with a compact macrocyclic structure designed to improve durability of response. TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK TKI, in adults with advanced solid tumors, including NTRK+ disease. The primary endpoint was confirmed objective response; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival and safety. Median follow-up ranged between 21.3 months and 25.7 months. In the TKI-naive cohort (n = 51; 95% confidence interval (CI)), the response rate was 59% (44–72); the median DOR was not estimable (NE); and the median PFS was 30.3 months (9.0–NE). In the TKI-pretreated cohort (n = 69; 95% CI), the response rate was 48% (36–60); the median DOR was 9.8 months (7.4–13.0); and the median PFS was 7.4 months (3.9–9.7). Of 30 TKI-pretreated patients with NTRK solvent front mutations, 16 had a response (53%; 95% CI: 34–72). Intracranial responses were observed in two of three TKI-naive patients and in four of six TKI-pretreated patients with measurable intracranial disease at baseline. Among all treated patients (n = 565), the most common any-grade treatment-related adverse event (TRAE) was dizziness (57%); most TRAEs were low grade; and 4% discontinued repotrectinib due to a TRAE. Overall, repotrectinib demonstrated durable systemic and intracranial responses with generally low-grade adverse events in patients with NTRK+ solid tumors, including those with previous TRK TKI treatment and solvent front mutations. These results support the use repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 .

  Study EGAS50000001572

• Molecular profiling of blastic plasmacytoid dendritic cell neoplasm (BPDCN) as compared to acute myeloid leukemia (AML)

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, male-predominant myeloid malignancy that is characterized by the malignant proliferation of precursor plasmacytoid dendritic cells (pDCs) with morphologic and molecular similarities to acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in its presentation within the bone marrow and peripheral blood. To identify disease-specific molecular features of BPDCN, we profiled bone marrow, peripheral blood and serum samples from primary patient samples using an in-house hematologic malignancy panel (“T300” panel), transcriptome microarray, and serum multiplex immunoassays and compared results to a cohort of AML patients.

  Study EGAS00001003453

• Sequence-Based Analysis of Human Breast Tumors

  The goal of this study is to study gene expression patterns in tumors, normal tissues, and cell lines.

  Study phs000676

• Kidney_tumour_DNA

  This is a bulk DNA and RNA sequencing study of human renal tumours

  Study EGAS00001002486

• Whole Exome Sequencing of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA.

  Whole Exome Sequencing of cohorts of Mutant Braf mouse model melanoma DNA and germline DNA. The cohorts are (1) Mutant Braf mouse model melanomas, (2) Mutant Braf mouse model melanomas from UVR exposed mice and (3) Mutant Braf mouse model melanomas from UVR exposed, sunscreen protected mice.

  Study EGAS00001000729

• Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

  Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.

  Study EGAS00001000942

• ATAC-seq iPSC cells or smNPC cells for allelic imbalance

  In order to confirm the predicted impact of the PD-associated allele of rs144814361 on BAG3 promoter, we proceeded with genome editing of the TH-REP1 cell line by using prime editing to insert the “T” allele at the position chr10:119651405 in the BAG3 promoter. 3 replicates for each condition: 1) iPSC Wild Type 2) SNP-BAG3 variant in iPSC 3) SNP-BAG3 variant in smNPC. Allelic imbalance is further assessed using read counting at this specific position.

  Study EGAS50000001579

• PacBio data of de novo assembly individual EGYPT

  This is the PacBio long read data used for performing de novo assembly of the EGYPT individual (mapped against GRCh38).

  Dataset EGAD00001006034

• TenK10K Phase 1: Whole Genome Sequencing Alignments

  Whole genome sequencing was performed for 1,925 samples from phase 1 of the TenK10K project. Sequencing was done with Illumina 2 x 150bp chemistry on a NovaSeq 6000 instrument to achieve mean 30x coverage. Sequence reads were aligned to the GRCh38 reference assembly with a fork of DRAGMAP v1.3.1. This dataset is comprised of 1,925 alignment files in cram format, and their corresponding index files.

  Dataset EGAD50000002466

• Raw RNA-seq data for clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

  ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint. This dataset includes the raw RNA-seq data.

  Dataset EGAD00001006205

• ATAC-seq of metastatic prostate tumors

  This dataset includes Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data, in FASTQ format, from 70 metastatic castration-resistant prostate cancer tumor samples from the SU2C/PCF West Coast Dream Team (WCDT) project. The sequencing data is paired-end, 150 bp sequencing data from an Illumina NovaSeq 6000 machine. ATAC-seq libraries were prepared following the protocol described in Buenrostro et al. Nature Methods. 2013 (PMID: 24097267) and Corces et al. Nature Methods. 2017 (PMID: 28846090).

  Dataset EGAD00001009654

• Maturation of Human Intestinal Epithelial Cell Layers Fortifies the Apical Surface against Salmonella Attack

  Pathogen invasion of intestinal epithelial cells (IECs) is a key gut infection event. The dynamics of this process in intact epithelia and the factors governing IEC susceptibility remain underexplored. We present a resource for live-cell infection imaging in human enteroid-/colonoid-derived IEC layers, across maturation states and in the presence or absence of soluble mucus production. Utilization of this resource shows how human IEC maturation fortifies the apical surface against invasion by Salmonella Typhimurium (S.Tm). Immature IEC layers appear permissive to S.Tm invasion, but maturation towards an enterocyte/colonocyte phenotype reduces the susceptibility by up to tenfold. This shift couples to downregulated expression of actin regulatory proteins exploited by the pathogen, an increased dependence on the S.Tm effector SipA, and the build-up of the apical IEC glycocalyx linked to surface-attached mucins like MUC13 and nullifiable by StcE-enzyme treatment. This underscores how the maturation state of human IECs governs susceptibility to bacterial invasion.

  Study EGAS50000001241

• Malignant progression of an ancestral bone marrow clone harboring a CIC-NUTM2A fusion in isolated myeloid sarcoma

  Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia (AML) or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow which carried the fusion despite the absence of pathology. Murine modeling confirmed the ability of the fusion to transform hematopoietic cells and identified receptor tyrosine kinase signaling activation consistent with disruption of the CIC transcriptional repressor. These findings extend the definition of CIC-rearranged malignancies to include hematologic disease, provide insight into the mechanism of oncogenesis, and demonstrate the importance of molecular analysis and tracking of bone marrow involvement over the course of treatment in myeloid sarcoma, including patients that lack flow cytometric evidence of leukemia at diagnosis.

  Study EGAS00001006833

• Cross-species Comparison Reveals Therapeutic Vulnerabilities Halting Glioblastoma Progression

  The growth of a tumor is tightly linked to the distribution of its cells along a continuum of activation states. Here, we systematically decode the activation state architecture (ASA) in a glioblastoma (GBM) patient cohort through comparison to adult murine neural stem cells. Modelling of these data forecast how tumor cells organize to sustain growth and identifies rate of activation as the main predictor of growth. Accordingly, patients with a higher quiescence fraction exhibit improved outcomes. Further, DNA methylation arrays enable ASA- related patient stratification. Comparison of healthy and malignant gene expression dynamics reveals dysregulation of the Wnt- antagonist SFRP1 at the quiescence to activation transition. SFRP1 overexpression renders GBM quiescent and increases overall survival of tumor-bearing mice. Surprisingly, it does so through reprogramming the tumor’s stem-like methylome into an astrocyte- like one. Our findings offer a framework for patient stratification with prognostic value, biomarker identification, and therapeutic avenues to halt GBM progression.

  Study EGAS00001008155

• Distinct genomic profiles and clinical outcomes in constitutional mismatch repair deficiency-associated high-grade gliomas: insights into mutational signatures and clonal evolution

  Constitutional mismatch repair deficiency (CMMRD) is a rare cancer-predisposition syndrome, yet the mutational processes and clonal evolution of CMMRD-associated high-grade gliomas (HGGs) remain incompletely understood. In this study, mutational signatures and tumor evolution were analyzed in 25 CMMRD-associated HGGs. Germline biallelic mutations were most frequently identified in MSH6 (56.0%), followed by PMS2 (36.0%) and MLH1 (8.0%). Affected patients showed very early disease onset (mean 5.8 years) and poor clinical outcomes, with a mean progression-free survival of 16 months. Distinct genomic and clinical differences were observed between MSH6- and PMS2-associated tumors. MSH6-deficient HGGs were enriched for SBS6, whereas PMS2-deficient tumors showed predominance of SBS21, and these mutational signatures were correlated with prognosis. Clonal evolution analyses revealed early involvement of POLE/POLD1 mutations and persistence of the founding clone at recurrence. Overall, the study highlights the importance of mutational signatures and clonal evolution in shaping tumor behavior and clinical outcomes in CMMRD-associated HGGs.

  Study EGAS50000001506

• Collection of Genotypic and Ethnographic Information from Individuals of South African Ethnic Groups

  The hunter-gatherers and pastoralists of South Africa retain the highest genetic diversity of any population. Genetic determinants of light skin pigmentation, reduced stature etc and other basic biomedical phenotypes are unique to samples with Southern African hunter-gatherer and pastoralist ancestry or retain ancestral haplotypes not found in other populations.

  Study EGAS00001004472

• exploration of biomarkers in colorectal cancer

  Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. To understand the molecular basis of colorectal cancer, we performed CAGE (Cap Analysis of Gene Expression) to quantify promoter activities on 45 colorectal cancers.

  Study JGAS000489

• Sequencing data from the study "Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer"

  This dataset consists of 71 whole-genome samples and 47 RNA-seq samples. All WGS samples are provided in .bam format and RNA-seq samples are provided as .fq.gz (paired-end). Next-generation sequencing data on whole genomes were processed by aligning sequencing reads to a reference genome (NCBI build 37/hg19) using bwa-mem (0.7.13-r1126).

  Dataset EGAD50000001978

• Bulk RNA sequencing data of high-grade serous ovarian cancer samples (set 18-19)

  The dataset contains RNA sequencing data of 66 high-grade serous carcinoma (HGSC) patients sequenced with Novoseq 6000. The 155 samples are fresh frozen tissue samples that have been collected from different tissues and time points before and during treatment. The files provided are paired fastq files.

  Dataset EGAD50000002370

• Clinical panel sequencing of cancer of unknown primary using TruSight Oncology 500 (TSO500)

  TruSight Oncology 500 (TSO500) cancer panel sequencing data on paired tumour and germline DNA from cancer of unknown primary samples. All of the samples in this dataset are matched to WGS data. This data was used to compare biomarker yield against what was achieved with WGS and contains n=51 tumour-only samples. All samples are in BAM format aligned with GRCh38 reference genome.

  Dataset EGAD50000000657

• Paroxysmal Neurological Disorders - rare epilepsies

  We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.

  Dataset EGAD00001000647

• GCAT| ICD Disease Diagnoses

  Disease diagnoses of GCAT Cohort participants obtained from electronic health records (EHR), mainly including the time period from 2012 to 2017. Disease diagnoses are codified in ICD-9, and the position of diagnosis refers to primary/secondary diagnoses (up to 14 secondary diagnoses per visit). The date and origin of the visit are also specified (AP: primary care, UGR: emergency, AH: hospital care, SMA: outpatient medical service, SMH: hospital medical service).

  Dataset EGAD00001007731

• Whole genome, whole exome and transcriptome sequencing of 10 ccRCC with Von Hippel-Lindau disease

  The aim of this study is to investigate genetic and transcriptomic profiles of inherited ccRCC with Von Hippel-Lindau disease.

  Study JGAS000544

• Genetic architecture of disease in Greenland is shaped by demographic history, fine-structure, and selection - WGS data

  This file set has 448 Greenlandic individuals sequenced using Illumina 150 Paired end sequencing and has an average sequencing depth of 35X. The data is unfiltered, in VCF format, and covers 19.751.308 variants.

  Dataset EGAD50000000933

• Cancer Genetic Markers of Susceptibility (CGEMS) Breast Cancer Genome-wide Association Study (GWAS) - Primary Scan: Nurses' Health Study - Additional Cases: Nurses' Health Study 2

  The initial stage of the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer genome-wide association study (GWAS) included genotyping 528,173 SNPs (Illumina HumanHap550) in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls from the Nurses' Health Study (NHS). Subsequently, incident invasive breast cancer cases from the Nurses' Health Study 2 (NHS2) cohort were genotyped using the Illumina HumanHap 610 quad. The NHS2 cases are younger than the cases in the first stage of the CGEMS breast cancer GWAS, which only included postmenopausal women. The NHS2 cases are a mix of pre- and postmenopausal women

  Study phs000147