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• Single cell TCRseq data fromTIL and non-TIL expanded TRACERx samples in the manuscript Bulk TCRseq from TRACERx samples from 'Subclonal immune evasion in non-small cell lung cancer'

  Immune checkpoint blockade in non-small cell lung cancer (NSCLC) rarely leads to complete tumour remission, suggesting that tumours harbour subpopulations of cancer cells that can escape immune predation. However, while tumours consist of multiple genetically distinct clones, the extent to which separate tumour subclones differ intrinsically in their functional capacity for immune evasion remains largely unexplored. This has been challenging to address due to an inability to isolate and propagate individual tumour subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived platform that allows the functional analysis of immune escape at single clone resolution. We generated libraries of >20 separate NSCLC organoid lines per patient by isolating individual (clonal) organoids established from multiple spatially separated tumour regions. Each organoid subline was co-cultured with autologous tumour infiltrating lymphocytes (TIL) to evaluate their capacity to elicit a T cell response. Organoid lines derived from separate tumour regions, or from single clones within individual regions, differ vastly in their capacity to elicit a T cell response, showing the coexistence of intrinsically immune evading (‘cold) and non-evading (‘hot) clones in the same primary tumour. Organoid lines escaping T cell recognition represent genetically and transcriptionally unique subclones with a distinct evolutionary history, showing that evolutionary sculpting of subclonal diversity can have functional consequences for anti-tumour immunity. Notably, the identification of immune-evasive subclones would not have been possible using computational approaches alone, highlighting the unique value of functional co-culture platforms. This patient-derived functional co-culture platform reveals that tumour evolution can give rise to distinct cancer clones with intrinsic differences in immune evasion capacity and provides an approach to prospectively identify, isolate and characterise immune evading subclones from patients with cancer.

  Study EGAS00001008161

• Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity

  Glioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primary IDH wild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.

  Study EGAS00001005227

• Single-Cell Transcriptomic Analysis of Kaposi Sarcoma

  Summary: Single-cell transcriptome analysis of skin and blood samples from individuals with Kaposi's sarcoma Aims: Elucidate the cellular composition and gene expression profiles of Kaposi sarcoma herpesvirus (KSHV) infected cells and non-infected tumor infiltrating cells, and peripheral blood samples from the same individuals, with or without specific therapies, such as antiretroviral therapy for HIV, immunotherapies (such as immune checkpoint inhibitors and immune modulator drugs like pomalidomide), or angiogenesis inhibitory agents. Population: Age 18 and older, both genders, including individuals from North America and other areas of the world (including Africa). Individuals with or without HIV are included. Molecular Technologies: Single-cell RNAseq using 10x Genomics Principal Findings: Two distinct populations of endothelial cells were found infected with KSHV, one CD34+ and one CD34-Both clusters include lytic and latent KSHV gene expressionThe KSHV infected cell clusters differ in expression of housekeeping genes, proliferative markers, ribosomal and secretory vesicle genesBiomarkers of KSHV infected cells were identified, including sodium channel SCN9A Changes in cell composition with therapy are noted Clonal amplification of TCR+ T-cells were noted in the skin and blood Data Available through dbGaP: scRNA-seq data

  Study phs003800

• Longitudinal RNA-seq datasets from patients after abdominal surgery

  This dataset consists of RNA-seq data of 126 whole-blood samples derived from patients after abdominal surgery. Total-RNA collected preoperatively and at 3-time points postoperatively (2-6, 24 and 48hrs) were analysed using RNA-sequencing. RNA was collected in PAXGene (Qiagen) tubes and extracted using the PAXGene RNA extraction kit, with a DNase step to remove contaminating DNA. Globin and ribosomal RNA were removed via a Ribo-zero kit (Illumina) and library preparation was carried out using the TruSeq Stranded Total RNA Library Prep Kit (Illumina). Next generation sequencing was performed on the NovaSeq sequencing platform (Illumina) at the Wellcome Centre for Human Genetics (WCHG) in Oxford.

  Dataset EGAD00001011102

• PanCancer_Phosphoproteomics2024

  Pan-cancer phosphoproteomics profiling data for 1000 retrospective and prospective samples of the MASTER/INFORM cohort,Shotgun proteomics

  Dataset EGAD00010002730

• AmsterdamUMC Data Access Committee for the study entitled "Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype"

  The current data access committee reviews and assesses data requests of researchers that seek to gain access to data presented in the manuscript entitled "Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype" as performed at the AmsterdamUMC, Amsterdam, Netherlands.

  Dac EGAC50000000178

• HIV-phyloTSI: PANGEA (PCR amplicon)

  This dataset includes sample numbers TSI_0426 to TSI_0527 for the PANGEA (PCR amplicon) cohort of the study. Samples were generated by pooling four overlapping PCR amplicons (see Gall et al 2012, DOI: 10.1128/JCM.01516-12). The sequencing was conducted using the Illumina NovaSeq system. Each sample has a BAM file, and its associated reference file.

  Dataset EGAD50000001308

• Small RNA sequencing from CSF extracellular vesicles - PD/CTR

  The dataset contains FASTQ files referring to the study "Small RNA sequencing from CSF extracellular vesicles - PD/CTR". For this project, RNA was isolated from CSF extracellular vesicles obtained by ultracentrifugation. Libraries were prepared with the TruSeq Small RNA library prep Illumina, and sequencing conducted in the Illumina HiSeq4000.

  Dataset EGAD00001006629

• Renal_habitat_WXS

  This project aims at correlating genetic diversity (as well as transcriptomic, metabolic and immune diversity) observed in multiple targeted tumour biopsies and circulating tumour DNA with heterogeneity on multiparametric MRI. To this end, 20 patients with RCC (15 patients with localised/locally advanced disease and 5 with mRCC) will undergo multiparametric MRI including metabolic assessment by 13C-MRSI as well as measurements of tumour perfusion, oxygenation and water diffusion. Based on unique combinations of these imaging parameters, tumour habitats will be defined through cluster mapping. Intra-operative biopsy and immediate freezing of tumour cores from different imaging habitats will be performed. Multiregional ex-vivo tumour biopsies will be spatially registered to the MR data by using 3D printed tumour moulds generated from high-resolution volumetric sequences. These moulds allow slicing tumour specimens in identical planes to the MR acquisition and increase the accuracy of tissue sampling. The biopsies will then undergo molecular profiling such as metabolomic and RNA sequencing (including mRNA immune profiling), as well as DNA sequencing to assess driver and clonal mutations in different tumour habitats and guide design of appropriate cfDNA probes. The targeted cfDNA capture panel will be employed to determine the ability of cfDNA to capture the full genetic diversity observed in the primary tumour and to relate cfDNA to various imaging habitats in both renal and pancreatic cancer. Data integration will be undertaken between imaging habitats and molecular profiles for each region.

  Study EGAS00001003703

• ATAC-seq data for two BCL11B-a subtype leukemia cases

  ATAC-seq was performed in two BCL11B-a subtype leukemia specimens to identify putative regulatory elements and allow comparison of motif enrichment in open chromatin to experimental and normal cell datasets. Raw paired-end reads were quality trimmed and adapter trimmed using TrimGalore (v0.4.4) with a quality score cutoff of Q20. The first 15 bp of each read were clipped to reduce the GC bias introduced by the Tn5 enzyme. Quality trimmed reads were mapped to the GRCh38 reference genome with BWA (v0.7.12-r1039) and converted to bam format using samtools64 (v1.2). Duplicate reads were marked using biobambam2 (v2.0.87). Bam files were submitted

  Dataset EGAD50000002472

• RNAseq and T cell receptor (TCR) profiling of PBMC cells 3 months post Omicron exposure

  This dataset contains RNA-seq and T cell receptor (TCR) sequencing files from a cohort (n=20) 3 months post positive PCR for SARS-CoV-2. A total of 10 hospitalised (samples H1-10) and 10 non-hospitalised (samples NH1-10) are contained within this dataset. RNA sequencing was performed using the Illumina Stranded mRNA Prep Ligation kit to investigate the protein coding transcriptome of PBMC cells. T cell receptor (TCR) repertoire profiling was performed with the TakaraBio SMART-Seq Human TCR (with UMIs) on PBMC cells to investigate the depth and persistence of SARS-CoV-2 targeting TCRs.

  Dataset EGAD50000001356

• RNA-seq and ATAC-seq data for ex vivo expanded T cells

  This dataset contains bulk RNA-seq and ATAC-seq data generated from naïve CD8+ T cells isolated from PBMCs of three healthy donors and stimulated ex vivo under multiple conditions. The dataset comprises 30 samples in total, including 15 RNA-seq samples and 15 ATAC-seq samples. Paired-end sequencing was performed on the Illumina NovaSeq 6000 platform. Raw data are provided as gzipped paired FASTQ files.

  Dataset EGAD50000002471

• Single-Cell DNA and Protein Sequencing Data from a Pediatric UBA1-Mutated MDS Patient

  This dataset contains raw single-cell DNA and protein sequencing data (FASTQ files) generated from a pediatric patient diagnosed with UBA1-mutated MDS. Samples were collected at two clinical timepoints and processed using single-cell DNA and Protein sequencing technology. The dataset includes paired-end sequencing reads for all libraries. Data are provided under controlled access through the associated Data Access Committee.

  Dataset EGAD50000002372

• Small RNA-Seq of MicroRNA's in extracellular vesicles of Ushers Syndrome patients

  Small RNA-Seq dataset of MicroRNA's found in tear extracellular vesicles (EVs) and hiPSC-derived retinal pigment epithelium (RPE) cells of Ushers Syndrome patients and control samples. 14 samples were isolated and assessed for quality before preparing libraries using the miReasy and TruSeq Small RNA Library Preparation Kit. Sequencing was performed on the Illumina NextSeq 2000 platform, generating paired end FASTQ files.

  Dataset EGAD50000001709

• Single-cell Transcriptomic and Immune Receptor Profiling of PBMCs from Dengue-Infected Individuals with Varying Disease Severities

  This dataset comprises single-cell RNA sequencing (scRNA-seq) and immune receptor (TCR/BCR) profiling of peripheral blood mononuclear cells (PBMCs) collected from individuals infected with dengue virus (DENV) exhibiting different clinical severities: asymptomatic dengue (AD), dengue fever (DF), and dengue hemorrhagic fever (DHF). PBMCs were collected during the acute phase and, in some cases, during convalescence. The data provide a resource for understanding protective versus pathogenic immune responses in dengue infection.

  Dataset EGAD00001015634

• The spatial organization of intratumor heterogeneity and evolutionary trajectories of metastasis in hepatocellular carcinoma

  A dataset consisting of Multi-regional Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) data for 54 samples from 9 patients with hepatocellular carcinoma. The dataset includes 45 tumor samples and 9 normal blood samples. Selected somatic variants were validated by Sequenom. Patients covered are: Patient 1, Patient 2, Patient 3, Patient 4, Patient 5, Patient 6, Patient 7, Patient 8, Patient 9 and Patient 10.

  Dataset EGAD00001003138

• snRNA-seq

  This dataset contains raw sequencing and processed data of single nuclei transcriptomes. The data were generated with 10x Chromium probe-based single-nucleus assay on FFPE tissues of 63 ST-EPN tumour resections. Raw data contain BAM (and BAM.BAI) files of the sequencing. Processed data contain aligned .h5 counts matrices as generated by 10x CellRanger for raw and filtered running options.

  Dataset EGAD50000001875

• Raw data (FASTQ) and processed data (VCF) of 7 patient-derived Sézary Syndrome (SS) cells

  We profile the whole-transcriptome (bulk RNAseq) of 7 patient-derived Sézary Syndrome (SS) cells to identify expression patterns, functional programs and expressed gene mutations that may provide clues on new therapeutic options for SS patients. The libraries were sequenced on NextSeq500 (Illumina) with a paired-end read length of 2x75bp. Raw data (FASTQ) and obtained processed data (VCF) including all called raw variants are available.

  Dataset EGAD50000001646

• Immunoglobulin Heavy-Chain locus in Multiple Sclerosis (n=4)

  Peripheral-blood or monocyte DNA from two healthy donors and two individuals with multiple sclerosis were sequenced on a PromethION-2 Solo (P2 Solo) instrument using R10.4.1 flow-cells and the Ultra-Long DNA Sequencing Kit (SQK-ULK114). For each participant we provide FASTQ reads (on-target), and haplotype-resolved assemblies of the complete IGH locus (~1.3 Mb) in FASTA format.

  Dataset EGAD50000001517

• Shallow whole genome sequencing DETECT samples

  Shallow whole genome sequencing of samples from the paper Beddowes et al. A large-scale retrospective study in metastatic breast cancer patients using circulating tumour DNA and machine learning to predict treatment outcome and progression-free survival. Mol. One 2025. This includes 1048 longitudinal plasma samples from 149 patients and 35 normals. Samples were sequenced with shallow whole genome sequencing for copy number estimation. All the files are single-end fastq files.

  Dataset EGAD50000001333

• Whole exome and targeted sequencing data from glioblastoma multiforme samples

  Whole exome and targeted sequencing data from 11 glioblastoma multiforme patients. A total of 70 tumour specimens and 11 blood samples were used for whole exome sequencing (WES) using the Agilent SureSelectXT Human All Exon V5 Kit. Two custom targeted sequencing panels were designed using the using Agilent’s Haloplex (TES1) or Agilent SureSelect XT2 technology (TES2). Libraries were sequenced on an Illumina HiSeq2500

  Dataset EGAD00001004420

• Transcriptome profiling of prostate tissue samples from early onset prostate cancer patients and normal controls by RNA-seq

  The dataset contains RNA-seq data of 96 EOPC patients and 9 controls. For some patients multiple tissue samples were sequenced ("multi-area" samples). The RNA extraction and sequencing protocol was earlier described in Weischenfeldt et al, Cancer Cell, 2013.

  Dataset EGAD00001004791

• RNA-seq of human glioblastoma and matched gliomasphere cell lines (BLN panel)

  This dataset contains all RNA-seq runs for the BLN panel of cell lines and matched parental tumors. Tumor/cell line pairs have been authenticated using SNP profiles and all pairs were confirmed. Please note: The dataset also contains raw data from an early primary culture (BLN-1) where no stable cell line could be generated. Please also note different reference genomes.

  Dataset EGAD00001002893

• Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases. Cancer Discovery doi: 10.1158/2159-8290. PMID: 30787016 PMCID: PMC6497554

  The BAM files for WES and RNA seq used in the article "Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases." on cancer Discovery 2019. PMID: 30787016 PMCID: PMC6497554. Authors : Grant M Fischer, ..., Michael A Davies.

  Dataset EGAD00001005046

• Molecular Evolution of Cancer

  Recently developed methods that utilize partitioning of long genomic DNA fragments, and barcoding of shorter fragments derived from them, have succeeded in retaining long-range information in short sequencing reads. These so-called read cloud approaches represent a powerful, accurate, and cost-effective alternative to single-molecule long-read sequencing. We developed software, GROC-SVs, that takes advantage of read clouds for structural variant detection and assembly. We apply the method to two 10x Genomics data sets, one chromothriptic sarcoma with several spatially separated samples, and one breast cancer cell line, all Illumina-sequenced to high coverage. Comparison to short-fragment data from the same samples, and validation by mate-pair data from a subset of the sarcoma samples, demonstrate substantial improvement in specificity of breakpoint detection compared to short-fragment sequencing, at comparable sensitivity, and vice versa. The embedded long-range information also facilitates sequence assembly of a large fraction of the breakpoints; importantly, consecutive breakpoints that are closer than the average length of the input DNA molecules can be assembled together and their order and arrangement reconstructed, with some events exhibiting remarkable complexity. These features facilitated an analysis of the structural evolution of the sarcoma. In the chromothripsis, rearrangements occurred before copy number amplifications, and using the phylogenetic tree built from point mutation data, we show that single nucleotide variants and structural variants are not correlated. We predict significant future advances in structural variant science using 10x data analyzed with GROC-SVs and other read cloud-specific methods.

  Study phs001255

• DAC Wachten Laboratory and Toma Laboratory, University of Bonn/University Hospital Bonn

  DAC for collaborative projects of the Wachten Laboratory (Institute of Innate Immunity, University of Bonn, University Hospital Bonn) and the Toma Laboratory (Institute of Pathology, University Hospital Bonn). Contact: Prof. Dr. Dagmar Wachten dwachten@uni-bonn.de Institute of Innate Immunity, University Hospital Bonn, University of Bonn, Germany Prof. Dr. Marieta I. Toma Marieta.Toma@ukbonn.de Institute of Pathology, University Hospital Bonn, Germany

  Dac EGAC50000000916

• Prospective Lynch Syndrome Database entries

  These data have been used to produce cancer incidence results for https://pubmed.ncbi.nlm.nih.gov/37181409/ , https://pubmed.ncbi.nlm.nih.gov/40231433/ and https://plsd.eu as available in March 2026. The tables contain demographic information at individual level, individual cancer events with given age, as well as prophylactic and therapeutic surgeries to remove organs. The data have been de-identified to ensure anonymity.

  Dataset EGAD50000002468

• TOTHER3 dataset

  This dataset contains the FASTQ and BAM files for TOTHER3 study. Targeted DNA-Seq experiment were realized with 49 samples. Since this data was obtained with a panel of genes protected by Intellectual Property (IP), these files only contain information to validate the results published and, in consequence, sensible data had to be specifically removed.

  Dataset EGAD50000000562

• MPM patients

  - RNA-sequencing data: 5 normal pleurae and 40 malignant pleural mesotheliomas - Targeted DNA-sequencing of the 165 genes included in the “Solid and Haematological tumors” panel (BRIGHTCore, Brussels, Belgium): 6 MPM samples. 2 FASTQ files for each sample (paired).

  Dataset EGAD00001008740

• INS01: Targeted sequencing of four tumours from a suspected VHL patient

  This dataset contains fastq files from four tumours that underwent targeted sequencing on panel for suspected VHL disease. The samples contained within the dataset and their corresponding sample ID are: ccRCC - M19-12422, Pheochromocytoma - M19-13800, Expelled lung tissue- M19-13801, and Liver biopsy- M19-13802.

  Dataset EGAD00001008438

• 666PG Whole genome alignment

  Aligned whole genome sequences in this dataset are from CPCG-GENE Normal/Tumor pairs used in the 666PG study. Raw sequences data was aligned against the human reference (GRCh37 + decoy) using bwa-mem and GATK for indel-realignment and recalibration

  Dataset EGAD00001004957

• Guardians_of_the_genome__protecting_DNA_from_endogenous_sources_of_damage_

  Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout.

  Study EGAS00001000800

• Genetics of non-syndromic idiopathic autism spectrum disorders in India

  The study explores the genetic architecture of patients diagnosed with non-syndromic autism spectrum disorders (according to the DSM-V criteria) in India. Patients were previously screened for aneuploidies using chromosomal G-banded karyotyping (at 500 band resolution) and Fragile-X using TP-PCR. Whole exome sequencing was performed on germline DNA from 100 idiopathic patients. Target enrichment was carried out using either Agilent SureSelect V6 or SureSelect Clinical Research Exome V2 kits. Pooled libraries were sequenced on Illumina HiSeq platform at an average coverage of 80-100x in 2x150bp configuration.

  Study EGAS00001006060

• Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas

  Supratentorial ependymomas (ST-EPNs) are aggressive and treatment-resistant pediatric brain tumors that form along the human cortex, with suspected origin from radial glia cells. Although histologically similar, ST-EPNs are molecularly classified into six distinct subgroups, many of them remaining understudied. Here, we integrated molecular cell states and spatial architecture to resolve the cellular origins and aberrant differentiation trajectories of ST-EPNs at single-cell resolution. We show that, while all ST-EPNs display a unified origin from neuroepithelial cells, different subgroups harbor highly diverse cell states and differentiation potential associated with neural or ependymal differentiation. Spatial mapping uncovered a higher-order structural tumor organization driven by presence of the mesenchymal state, and refines classical histological features based on detailed molecular resolution. By benchmarking a morpho-molecular cell-state classification system in different disease models and human tumors, we identified four cellular subtypes defined by the architecture of neurite-like extensions that mediate either self-renewal or fast, saltatory invasive phenotypes reminiscent of neurons during neurodevelopment. Collectively, our study provides a comprehensive framework for the study of ST-EPN cellular states, and reveals biologically relevant tumor compartmentalization with potential clinical implication.

  Study EGAS50000001513

• Small RNA sequencing of human oocytes and early embryos

  This dataset contains single-end fastq files for human oocytes (n=12), zygotes (n=5), and early embryos (n=10) sequenced with Illumina NextSeq500. The sequencing libraries were prepared from single oocytes, zygotes, and embryos in two batches.

  Dataset EGAD50000000227

• cell-free methylated DNA immunoprecipitation and high-throughput sequencing data for samples from liver transplant recpients with graft pathologies

  Bam and indexed bam files after removal of duplicates and trimming of the unique molecular identifiers. Sequencing was performed on NovaSeq 6000 platform.

  Dataset EGAD00001010305

• Dataset for RNA and Exome sequencing of Glioblastoma samples

  This dataset contains RNA Seq, 10x scRNA Seq and Exome sequencing of glioblastoma samples. Sequencing was performed on a Illumina NovaSeq 6000 and Illumina HiSeq 4000. The sequencing was always paired.

  Dataset EGAD00001012235

• November 2020 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  November 2020 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001007529

• Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple negative breast cancer: phase 2 adaptive BELLINI trial. RNA-Seq

  The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary endpoint: two-fold increase in CD8+ T cells or IFNG), providing rationale for neoadjuvant ICI without chemotherapy. In window of opportunity cohorts A (4 weeks anti-PD1) and B (4 weeks anti-PD1 + anti-CTLA4), we observed immune activation in 53% (8/15) and 60% (9/15) of patients, respectively. High tumor-infiltrating lymphocytes (TILs) correlated with response. Based on these data, we opened cohort C for patients with high TILs (≥50%) who received 6 weeks neoadjuvant anti-PD1 + anti-CTLA4 followed by surgery (primary endpoint: pathological complete response, pCR). 53% (8/15) of patients had major pathological response (< 10% viable tumor) at resection, with 33% (5/15) having pCR. All cohorts met Simon’s two-stage threshold for expansion to stage II. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early TNBC.

  Study EGAS50000000567

• Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple negative breast cancer: phase 2 adaptive BELLINI trial. WES

  The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary endpoint: two-fold increase in CD8+ T cells or IFNG), providing rationale for neoadjuvant ICI without chemotherapy. In window of opportunity cohorts A (4 weeks anti-PD1) and B (4 weeks anti-PD1 + anti-CTLA4), we observed immune activation in 53% (8/15) and 60% (9/15) of patients, respectively. High tumor-infiltrating lymphocytes (TILs) correlated with response. Based on these data, we opened cohort C for patients with high TILs (≥50%) who received 6 weeks neoadjuvant anti-PD1 + anti-CTLA4 followed by surgery (primary endpoint: pathological complete response, pCR). 53% (8/15) of patients had major pathological response (< 10% viable tumor) at resection, with 33% (5/15) having pCR. All cohorts met Simon’s two-stage threshold for expansion to stage II. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early TNBC.

  Study EGAS50000000568

• Clonal Evolution and Transcriptomic Analysis of Chronic Lymphocytic Leukemia Treated with Ibrutinib

  Disease progression has been increasingly appreciated with the use of ibrutinib to treat chronic lymphocytic leukemia (CLL). Understanding the pattern of clonal evolution and transcriptomic changes during the early treatment period with ibrutinib may provide insight into the mechanisms of resistance. We performed whole exome sequencing on sequential samples with matched germline controls from 61 patients with CLL during the first 12 months of ibrutinib monotherapy or ibrutinib in combination with rituximab. Additionally, RNA sequencing was done on a subset of 14 patients treated with ibrutinib monotherapy. The presence of clonal shifts was associated with an increased risk of disease progression, suggesting that resistant clones are more likely to emerge in CLL with greater evolutionary capacity.This cohort was later augmented with additional data (including data from 15 additional patients). In total, this second set of data contained whole exome sequencing (31 samples), RNA sequencing (6 samples) and reduced representation bisulfite sequencing (67 samples) for CLL samples and used them to identify expression subtypes of CLL. In an integrative analysis of genetic, transcriptomic, and epigenetic data, incorporating known and newly identified subtypes of CLL, we built new models to improve patient prognostication.

  Study phs001473

• Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors

  Cell-free tumour-derived DNA (ctDNA) allows non-invasive monitoring of various cancers but its utility in renal cell cancer (RCC) has not been well established. A combination of untargeted and targeted sequencing methods, applied to two independent cohorts of patients (n=90) with various renal tumour subtypes, were used to determine ctDNA content in plasma and urine. Our data revealed lower plasma ctDNA levels in RCC relative to other cancers, with untargeted detection of ~33% for both cohorts. A highly sensitive personalised approach, applied to plasma and urine from select patients (n=22), improved detection to ~50%, including in patients with early stage and even benign lesions. A machine-learning based model, applied to untargeted data, predicted this detection, potentially offering a means of triaging patient samples for personalised analysis. We observed that plasma, and for the first time, urine ctDNA may better represent tumour heterogeneity than a single tissue biopsy. Longitudinal sampling of &gt;200 plasma samples revealed that ctDNA can track disease course. These data highlight low ctDNA levels in RCC but indicate potential clinical utility provided improvement in isolation and detection approaches.

  Study EGAS00001003530

• Complex genotype-phenotype relationships shape the response to treatment of Down Syndrome Childhood Acute Lymphoblastic Leukaemia

  Extensive genetic and epigenetic variegation has been demonstrated in many malignancies. Importantly, their interplay has the potential to contribute to disease progression and treatment resistance. To shed light on the complex relationships between these different sources of intra-tumour heterogeneity, we explored their relative contributions to the evolutionary dynamics of Acute Lymphoblastic Leukaemia (ALL) in children with Down syndrome, which has particularly poor prognosis. We quantified the tumour propagating potential of genetically distinct sub-clones using serial transplantation assays and SNP-arrays. While most leukaemias were characterized by a single dominant subclone, others were highly heterogeneous. Importantly, we provide clear and direct evidence that genotypes and phenotypes with functional relevance to leukemic progression and treatment resistance can co-segregate within the disease. Hence, individual genetic lesions can be restricted to well-defined cell immunophenotypes, corresponding to different stages of the leukemic differentiation hierarchy and varied proliferation potentials. As a result of this difference in fitness, which can be accurately quantified via competitive transplantation assays, matching diagnostic, post-treatment, and relapse leukaemias can be dominated by different genotypes, including pre-leukemic clones persisting throughout the disease progression and treatment. Intriguingly, plasticity also appears to be a temporally defined property that can segregate with genotype. These results suggest that Down Syndrome ALL should be viewed as a complex matrix of cells exhibiting genetic and epigenetic heterogeneity that foster extensive clonal evolution and competition. Therapeutic intervention reshapes this ‘eco-system’ and may provide the right conditions for the preferential expansion of selected compartments and subsequently relapse.

  Study EGAS50000001287

• Genetic and Hormonal Contributions to Gene Expression in Immune Cells

  The origins of sex differences in human disease are elusive, in part because of difficulties in separating the effects of sex hormones and sex chromosomes. To isolate the effects of testosterone, estradiol, and sex chromosome complement (XX or XY) in humans, we implemented a four-state, cross-sectional study design of trans- and cisgender individuals, the former receiving exogenous testosterone or estradiol for at least a year as part of their gender-affirming medical care. This study design allowed us to compare four combinations of sex hormones and sex chromosomes in humans: XX individuals treated with exogenous testosterone (n=21), XY individuals treated with exogenous estradiol (n=13), untreated XX individuals (n=20), and untreated XY individuals (n=15). We chose to focus on the human immune system because it displays an impressively broad range of sex-differential biology. We collected blood samples from each individual and isolated PBMCs the same day. We performed 10X Genomics 3&#39; single-cell RNA-sequencing (scRNA-seq) on PBMCs from the 69 individuals. We generated 150-bp paired end reads from a total of 358,426 cells (with an average of 48,007 reads/cell) and identified 18 distinct immune cell types. We found that testosterone, estradiol, and sex chromosome complement have unique, non-overlapping effects on PBMC cell abundances and gene expression.

  Study phs003860

• Molecular Sub-grouping of CNS-PNET

  In our study we aimed to define CNS-PNET subgroups. We performed Expression, Genotyping and/or Immunohistochemistry on 142 samples from 20 worldwide centers. Using these techniques, we have identified three molecular subgroups with distinct expression and copy number patterns, as well as, unique clinical characteristics. Specifically, these molecular subgroups were distinguished by primitive neural (group 1), oligoneural (group 2), and mesenchymal lineage (group 3) gene-expression signatures with differential expression of cell-lineage markers LIN28 and OLIG2. Our report underscores the importance of concerted, collaborative efforts to study large retrospective cohorts of tumours and patients to accelerate biological and ultimately therapeutic studies of rare tumours. The outcome of such a collaboration allowed us to identify LIN28 and OLIG2 as promising diagnostic and prognostic molecular markers for CNS PNET that warrant further assessment in prospective clinical trials.

  Study EGAS00000000116

• Dataset of 10 WES from bladders tumors and PBMC of 4 non-muscle invasive bladder cancer patients

  WES (FASTQ files) of paired tumor and PBMC samples of non-muscle-invasive bladder cancer patients. All CTRL samples originate from PBMC. For patient UC2, DNA from 3 different synchronous tumors were extracted. DNA from tumors was extracted from fresh frozen tumors,except for patient UC4 (FFPE). NB : patients aliases are the following :ROXY : UC1, OMAD : UC2, MAKI : UC3, HAPE : UC4

  Dataset EGAD50000002008

• Genomic Data for Integrative Profiling of T790M Negative EGFR Mutated NSCLC

  Contains WES and RNA-seq for the 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC.

  Dataset EGAD00001010272

• Fetal body map

  From 2nd trimester human foetuses we derived liver and intestinal stem cells. These were clonally expanded until enough material was available for whole genome sequencing. For each foetus, reference tissue (skin or bulk liver) was also sequenced to determine all germline variants. These were subtracted from the clones to determine all somatic mutations that had been acquired during embryonic and fetal development.

  Dataset EGAD00001003997

• Genomic Characterization of Duke Melanoma Brain Metastases

  Previous work has shown that melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biology of MBM and associations between biological features and clinical outcomes will facilitate the design of rational therapies for patients with MBM. To better characterize the molecular profile of MBM, we conducted whole exome sequencing (WES) and total RNA sequencing on MBM tissues obtained from an independent cohort of 14 patients from Duke University Medical Center. This cohort adds valuable patient samples to the field and enables strengthened investigation of somatic mutations and gene expression profiles within and between cohorts. The mutational landscape and gene expression of MBM from the Duke cohort resembled those previously reported in a previously published dataset of WES and RNA sequencing in MBM and matched ECM tissues from UT MD Anderson Cancer Center (Fischer et al., 2019 30787016). Duke MBM demonstrated similar rates of mutations in genes associated with melanoma, including BRAF, NRAS, and PTEN, as the MD Anderson cohort. Immune populations in MBM were similar between Duke and MD Anderson MBM, though Duke samples demonstrated more resting CD4+ memory T cells. The ratio of M2 to M1 macrophages in the Duke cohort was similar to that of the MD Anderson cohort. In MBM, a higher M2:M1 ratio may contribute to an immune-suppressive tumor microenvironment. Sequencing data and sample attributes from MBM tissues obtained from 14 patients from Duke University Medical Center will be available through dbGaP.

  Study phs003009

• Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) - Genome-Wide Association Study Meta-Analysis

  Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) was one of five projects funded in 2010 as part of the NCI&#39;s Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (http://epi.grants.cancer.gov/gameon/). GAME-ON&#39;s overall goal was to foster an intra-disciplinary and collaborative approach to the translation of promising research leads deriving from the initial wave of cancer GWAS. Specific goals included replication of previous GWAS findings and identification of new susceptibility loci through meta analyses of existing GWAS data and fine mapping of identified loci to better pinpoint causal variants; and identify germline variants that are associated with risk of multiple cancers. The other four funded GAME-ON projects were: the ColoRectal TransdisciplinaryStudy (CORECT), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), Follow-up of Ovarian Cancer Genetic Association and Interaction Study (FOCI), and Transdisciplinary Research in Cancer of the Lung (TRICL). To identify additional cancer risk loci, improve the precision of fine-mapping, and facilitate cross-cancer analyses, DRIVE investigators performed a meta-analysis of eleven genome-wide association studies of breast cancer: The Australian Breast Cancer Family Study (ABCFS), the British Breast Cancer Study (BBCS), the Breast and Prostate Cancer Cohort Consortium (BPC3), the Breast Cancer Family Registries (BCFR), the Dutch Familial Bilateral Breast Cancer Study (DFBBCS), German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), the Helsinki breast cancer family Study (HEBCS), the Mammary Carcinoma Risk factor Investigation (MARIE), the Singapore and Sweden Breast Cancer Study (SASBAC), the Triple Negative Breast Cancer Study (TNBC), and the UK2 GWAS. These studies comprised a total of 16,062 cases and 46,157 controls. Imputation to the 1,000 Genomes Project Phase 1 v3 ALL reference panel was performed by study, and summary statistics from each study were combined using fixed-effect meta analysis.

  Study phs001263