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• Human tumor bulk RNA-seq

  We profiled 186 patient tumor samples by bulk RNA-seq. These includes 38 embryonal brain tumors, 101 high-grade gliomas, 24 low-grade gliomas, 10 medulloblastoma and 13 matched normals. The raw fastqs are provided.

  Dataset EGAD00001005131

• Copy number profiling of tissue and plasma samples from high grade serous epithelial ovarian cancer patients

  This dataset includes 289 samples from 46 high grade serous epithelial ovarian cancer patients. Data are from both tissue samples (either primary tumor, or synchronous metastases) and circulating cell-free DNA (cfDNA) of plasma samples taken during therapy and follow-up.

  Dataset EGAD00001006422

• RNA-seq cohort of normal weight women

  RNA-seq data of non-tumorous breast tissue. There are 32 samples in this cohort.

  Dataset EGAD00001007073

• Single cell TCR Analysis of regulatory Tcells from blood, fat and skin

  Regulatory Tcells were FACS sorted and processed with 10x Genomics Chromium Next GEM SingleCell V(D)J Reagents Kits v1.1 sequencing. In total 17 samples were processed. Fastq files are supplied.

  Dataset EGAD00001007661

• 4C-seq in endometrial healthy and tumor tissues

  4C-seq performed on 10 slices (30um thick) of fresh frozen endometrial tissues. These tissue include 2 healthy tissues and 4 tumor tisseus (post-menopausal patients) in replicate. The library has been performed using DpnII (primary) and NlaIII (secondary) restriction enzymes. Raw single-end fastq.gz files are provided.

  Dataset EGAD00001010897

• MATISSE Whole-exome sequencing data

  Sample availability: WES was performed on 41 available baseline tumor and blood samples (22 CCRs/MPRs, 5 PPRs, 14 CRN/NPRs). Tumor DNA was extracted from formalin-fixed paraffin-embedded (FFPE) primary tumor and lymph node metastasis sections containing at least 10% viable tumor cells present in the sample. A pathologist (LS) scored the tumor percentage and indicated the most tumor-dense region on a hematoxylin and eosin (H&E) stain slide for subsequent DNA isolation. According to the manufacturer's protocol, five to 10 FFPE slides (10 µm) were used for DNA isolation using the AllPrep DNA FFPE isolation kit (Qiagen, 80234) and the QIAcube. Germline DNA was isolated from baseline PBMCs using the AllPrep DNA / RNA / miRNA Universal isolation kit (Qiagen, 80224) and the QIAcube, according to the manufacturer’s protocol. Genetic Diagnostics and Sequencing Services (CeGaT) performed whole-exome sequencing sequencing in Germany. Data processing: Demultiplexing of the sequencing reads was performed with Illumina bcl2fastq (v2.20). Adapters of the reads were trimmed with Skewer (v0.2.2), without quality trimming. Sequencing reads were aligned with BWA (v0.7.17) to the human reference genome GRCh38 (Ensemble, v105). Duplicated reads were marked using Picard (v2.25.0) MarkDuplicates, after which quality scores were recalibrated using GATK4 (4.2.2.0) BaseRecalibrator. FastQC (v0.12.1), MultiQC (v1.14), Mosdepth (v0.3.3) and NGScheckmate (v1.0.1) were used for assessing data quality, on FASTQ files and intermediate processing steps.

  Dataset EGAD50000001469

• EPIC arrays data for chemotherapy response project

  In this study, a total of 300 patients with MIBC receiving chemotherapy were included; 62 received NAC before cystectomy and 245 received first-line chemotherapy upon detection of locally-advanced (T4b) or metastatic disease. Treatment response, defined as pathological downstaging (< pTa,CIS,N0) after NAC or complete or partial response after first-line treatment (RECIST criteria). DNA methylation analysis was performed using DNA from 72 patients. We used 500 ng genomic DNA for bisulfite conversion followed by whole-genome amplification prior to hybridization to EPIC BeadChip (Illumina, San Diego, CA) overnight as described by the manufacturer and then scanned with the Illumina iSCAN system. Data provided here consist of 144 idat files.

  Study EGAS00001004515

• TB-DAR Whole Genome Sequencing Study

  116 Whole Genome Sequencing (WGS) samples from the TB-DAR study, based on a cohort of adult pulmonary tuberculosis patients recruited in Dar es Salaam, Tanzania. WGS was performed at the Health2030 Genome Center in Geneva on the Illumina NovaSeq 6000 instrument (Illumina Inc, San Diego CA, USA), starting from1μg of whole blood genomic DNA and using Illumina TruSeq DNA PCR-Free reagents for library preparation and the 150nt paired-end sequencing configuration. Average coverage was above 30X for 75 samples, between 10X and 30Xfor 40 samples, and approximately 8X for a single sample. Sequencing reads were aligned to the GRCh38 (GCA_000001405.15) reference genome using bwa (Version 0.7.17).

  Dataset EGAD00001008400

• The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients

  Telomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rates and spectrum of somatic TFs across >30 cancer types using whole-genome sequencing data. TFs are pervasive in human tumours with rates varying markedly across and within cancer types. In addition to end-to-end fusions, we find novel patterns of TFs that we mechanistically link to the activity of the alternative lengthening of telomeres (ALT) pathway. We show that TFs can be detected in the blood of cancer patients, which enables cancer detection with high specificity and sensitivity even for early-stage tumours and cancers of high unmet clinical need. Overall, we report a novel genomic footprint that enables characterization of the telomere maintenance mechanism of tumours and liquid biopsy analysis.

  Dataset EGAD00001012101

• Accurate Immune Repertoire Sequencing Reveals Malaria Infection Driven Antibody Lineage Diversification in Young Children

  This study describes a novel Immune Repertoire Sequencing technique, termed Molecular Identifier Clustering-based Immune Repertoire Sequencing (MIDCIRS), to reduce sequencing error while maintaining extremely high coverage and applies this technique to investigate the differential immune response to malaria between infants and toddlers. Despite a lower somatic hypermutation load, we found an unexpectedly high level of competency within the infant antibody repertoire, particularly the ability to diversify B cell clonal lineages upon acute infection. Detailed clonal lineage analysis encompassing lineages containing sequences from both pre- and acute malaria timepoints revealed an increase in somatic hypermutations upon acute infection. Further analysis on pre-malaria memory B cell containing lineages in toddlers who had previously been exposed to malaria provides evidence for the capacity of memory B cells to continue to mutate and isotype switch.

  Study phs001209

• Genome-wide Association Study and Meta-Analysis of Ewing Sarcoma

  We combined a set of 122 French Ewing sarcoma (EWS) cases from the Institut Curie, 19 EWS cases from the National Cancer Institute (NCI) Center for Cancer Research (CCR), and 29 EWS cases from the NCI Bone Disease and Injury Study. All EWS cases were confirmed by medical record review and the presence of a specific EWSR1-ETS translocation were noted when data was available. Each participant provided informed consent and each participating study was approved by the Institutional Review Boards of their study center. DNA was extracted using standard methods from blood, saliva (Oragene), or buccal cells. All de novo genotyping of EWS cases was performed at the NCI CGR on the Illumina OmniExpress-24 v1.1 array. Genotyping was performed according to manufacturer's guidelines using the Infinium HD Assay automated protocol.

  Study phs001549

• Sequencing Lymphoma

  This repository contains sequencing data to describe the genomic profiles of several B-cell lymphomas including follicular lymphoma and Hodgkin lymphoma. We have used several different high throughput sequencing technologies to interrogate genomic DNA and RNA from tumor cells obtained from lymph node biopsies and normal cells obtained from skin biopsies and peripheral blood mononuclear cells. A number of sequencing platforms for DNA, RNA, and protein were used to generate the data. These platforms include exome sequencing and a custom capture panel (NimbleGen) that targets 7.05 MB corresponding to the exons and splice sites of 1716 genes related to lymphoma biology (WUSM-LP). Other platforms include single-cell RNA-seq and Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), which was used to describe transcriptional and proteomic changes in immune cell subsets within lymphoma patients pre- and post-therapy.

  Study phs001229

• Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions

  In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has killed hundreds of thousands of people, including >23,000 in New York City (NYC) alone. The pandemic's sudden emergence highlights the clinical need to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we provide large-scale shotgun metatranscriptomics (total-RNA-seq) for host, viral, and microbial profiling. In version 1, we sequenced a total of 732 clinical specimens (nasopharyngeal (NP) swabs) gathered from 669 unique patients in New York City during the first two months of the outbreak. In version 2, we sequenced an additional 168 clinical specimens from autopsy tissues (lung, heart, kidney, liver, and lymph node) from 60 patients, yielding a broad molecular portrait of the emerging COVID-19 disease across 900 clinical specimens and 729 patients.

  Study phs002258

• RNA Ligation Precedes U6 snRNA/LINE-1 Retrotransposition

  Long Interspersed Element-1 (L1) retrotransposons make up approximately 17% of the human genome. L1 moves throughout the genome via a copy-and-paste mechanism termed retrotransposition. L1 retrotransposition also mobilizes other cellular RNAs such as SINES, U6 snRNA and, mRNA, which for the latter results in the formation of processed pseudogenes. In this study we demonstrate that the RNA ligase RtcB can create chimeric RNAs by joining U6 snRNAs to 5'-truncated L1 or other cellular RNAs. We also show that the retrotransposition of U6/L1 chimeric RNA leads to U6/L1 pseudogene formation. In sum, our data suggests that U6 snRNA and RtcB may have biological roles in addition to their essential functions in mRNA and tRNA splicing, and that the retrotransposition of chimeric RNAs could be a mechanism to create novel genes.

  Study phs001671

• Longitudinal single-cell transcriptomic study in patient-derived xenografts of pediatric T-ALL

  In this study, we conducted single cell full length total RNA sequencing (VASA-seq) on 13 matched pediatric T-ALL PDX samples at initial diagnosis and relapse, along with 5 non-relapsing PDX samples collected at initial diagnosis. We identified a subpopulation of T-ALL cells with stem-like cell features that expands substantially at relapse indicating resistance to first-line therapy. Chemotherapy resistance was further validated through functional testing: Two samples were subjected to in-vitro drug testing, treated with Cytarabine for three days, followed by single-cell transcriptomic analysis using 10x Genomics. Additionally, in-vivo drug testing was conducted on one sample, involving re-engraftment into mice and treatment with a combination of Vincristine, Doxorubicin, and Dexamethasone. Single-cell transcriptomic analysis using 10x Genomics was performed after 0, 15 and 30 days of treatment.

  Study EGAS50000000582

• ATAC-Seq of healthy and IBD blood samples

  PBMCs from blood samples of 9 age- and gender-matched healthy subjects and 25 IBD patients were isolated through a Ficoll density gradient and used to isolate live CD4 T cells through a magnetic cell isolation kit (Miltenyi Biotec). Twelve thousand live CD4 T cells were then used to prepare ATAC-Seq libraries. Briefly, crude nuclei of live CD4+ T cells were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.

  Study EGAS00001007343

• single nuclei RNASeq of 5 regions of the human prenatal brain

  Data generated through single nuclei RNA sequencing on 5 regions of the brain (frontal cortex, ganglionic eminence, hippocampus, thalamus and cerebellum) from 3 fetuses (two of 14 and one of 15 post-conception weeks, all female). Tissue was acquired from the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR) with ethical approval. snRNA-seq libraries were prepared from ∼10,000 nuclei from each sample using Chromium Single Cell 3ʹ (v3) reagents (10X Genomics). Quality control of libraries was performed using the Agilent 5200 Fragment Analyzer before sequencing on an Illumina NovaSeq 6000 to a depth of at least 865 million (median = 1.01 billion) read pairs per library. Raw sequencing data were converted into FASTQ files. For a full description of data generation, please see Cameron et al, Biological Psychiatry 2022, https://doi.org/10.1016/j.biopsych.2022.06.033.

  Study EGAS00001006537

• Detecting and quantifying clonal selection in somatic mosaicism

  In this study, we introduce a scalable method to identify clonal selection in an individual tissue, agnostic of the underlying mutations. To study clonal selection in the haematopoietic system, we performed whole genome sequencing on bone marrow CD34+ haematopoietic stem and progenitor cells from 22 non-leukemic individuals, 30-89 years of age. We performed 90x whole genome sequencing for all samples and re-sequenced 19 samples with sufficient DNA to a total target coverage of 270x. Whole genome sequencing of hair follicle DNA from the same individuals was used as germline control. In addition, we sequenced unseparated bone marrow mononuclear cells, CD3-CD34- bone marrow mononuclear cells, and peripheral blood granulocytes from 14 samples. Samples were collected from individuals undergoing hip replacement surgery as part of the Mechanisms of Age-Related Clonal Haematopoiesis (MARCH) Study (REC Ref: 17/YH/0382).

  Study EGAS00001007558

• Targeted sequencing of breast cancer susceptibility genes for 1,995 Japanese breast cancer patients

  In this study, we investigated pathogenic germline variants in 11 genes implicated in hereditary breast cancer, including BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, NF1, PALB2, ATM, CHEK2, NBN1, in a total of 1,995 unselected Japanese women with breast cancer using targeted-capture sequencing of pooled DNA (n = 106).

  Study EGAS00001004630

• TMD-AMKL targeted follow-up part 2

  Genomic libraries will be generated from total genomic DNA derived from 200+ patients with childhood Transient Myeloproliferative Disorder (TMD) and or Acute Megakaryocytic Leukemia (AMKL) as well some matched constitutional samples (n < 50). Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 96 Samples will be individually barcoded and subjected to up to two lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.

  Dataset EGAD00001000879

• Targeted sequencing of genes recurrently mutated in AML - part2

  Genomic libraries will be generated from total genomic DNA derived from 4000 samples with Acute Myeloid Leukaemia. Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 64 Samples will be individually barcoded and subjected to up to one lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.

  Dataset EGAD00001000747

• Comprehensive copy number aberration analysis using digital Multiplex Ligation-dependent Probe Amplification (digitalMLPA) in pediatric B-cell precursor acute lymphoblastic leukemia

  In this study a next-generation sequencing based method was applied to comprehensively screen for recurrent, disease-relevant copy number aberrations in a cohort of Hungarian patients. Diagnostic bone marrow samples from 260 children with B-cell acute lymphoblastic leukemia as well as 72 control samples and were investigated by digital multiplex ligation-dependent probe amplification using the disease-specific D007 probemix. Whole chromosome gains and losses, as well as subchromosomal copy number aberrations were simultaneously profiled.

  Dataset EGAD00001010878

• TNBC ctDNA Targeted Panel

  Circulating tumour DNA (ctDNA) detection in liquid biopsy is an emerging alternative to tissue biopsy, but its utility in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) remains to be well understood. In this study, we determined the presence of early stage TNBC ctDNA detectable actionable mutations with a clinically validated hotspot treatment indication panel. Sequencing of plasma DNA from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in NAT protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

  Study EGAS00001006937

• Stereotyped B-cell responses are linked to IgG constant region polymorphisms in multiple sclerosis

  Clonally related B cells infiltrate the brain, meninges, and cerebrospinal fluid of multiple sclerosis (MS) patients, but the mechanisms driving the B-cell response and shaping the immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq and B-cell receptor reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy- and light-chain repertoires in intrathecal B cells. We detected extensive clonal connections between the memory B cell and antibody-secreting cell compartments and observed clonally related cells of different isotypes, including IgM/IgG1, IgG1/IgA1, IgG1/IgG2, and IgM/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in antibody-secreting cells, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the immunoglobulin heavy-chain variable (IGHV)4 gene family with the κ variable (IGKV)1 gene family. The IGHV4-39 gene was most used and showed the highest frequency of pairing with IGKV1-5 and IGKV1(D)-33. These results link IgG constant region polymorphisms to stereotyped B-cell responses in MS and indicate that the intrathecal B-cell response in these patients could be directed against structurally similar epitopes.

  Study EGAS00001005745

• Spatial Transcriptomic Analysis (Xenium in situ) of Large Cell Neuroendocrine Carcinoma

  Lung LCNEC (Large Cell Neuroendocrine Carcinoma) has a poor prognosis, and no effective treatment has yet been established. We have discovered that LCNEC exhibits highly heterogeneous distribution of proteins such as neuroendocrine markers and YAP1 within the tumor. We hypothesize that this heterogeneity may be responsible for the variability in chemotherapy effectiveness and treatment resistance among LCNEC patients. Therefore, by using Xenium to analyze gene expression in greater detail along with tumor morphology, we aim to identify new characteristics of LCNEC and explore potential treatment strategies.

  Study JGAS000733