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• Whole-Genome sequencing of hepatocellular carcinomas

  The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors using whole genome and whole exome sequencing together with CGH-SNP, methylome and transcriptomic profiling. For this purpose, a series of 500 liver tumors are collected through the French National Liver Collection and these samples will be analyzed using the different omics technologies. The data will be deposited in the ICGC and EGA database to be publically available for the scientific community. Hepatocellular carcinoma (HCC) accounts for more than 90% of liver cancers, and is a major health problem. It is the 3rd cause of cancer-related mortality. Advances in genomic analyses have formed a comprehensive understanding of different underlying pathobiological layers resulting in hepatocarcinogenesis. Thus, the development of next-generation sequencing technologies has made it possible to generate more comprehensive catalogues of somatic alteration events (single nucleotide substitutions, structural variations, and epigenetic changes) in liver cancer genome than ever before. The dataset will include 50 whole genome sequencing tumor/germline pairs, of which 6 are deposited in February 2014.

  Study EGAS00001000706

• Direct Detection of Early-stage Cancers Using Circulating Tumor DNA

  Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.

  Study EGAS00001002577

• WGS of 32 paired SRCC samples

  Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however with no systematical investigation for prognostic genomic features. We systematically investigated the clinical characteristics of 1,868 Chinese gastric cancer patients, and found that signet-ring cell content was significantly related to multiple clinical characteristics and treatment outcomes. Next, we performed whole genome sequencing for 32 SRCC patients with > 80% signet-ring cells in tumor, and identified frequent5 CLDN18-ARHGAP26/6 fusion (25%). With additional 797 patients for validation, we notice that prevalence of CLDN18-ARHGAP26/6 fusion is positively associated with signet-ring cell content (P = 4.1 x 10 -9 ), younger age at diagnosis (P = 4.2 x 10 -10 ), female/male ratio (P = 1.7 x 10 -9 ), and advanced TNM stage (P = 1.7 x 10 -5 ). Importantly, patients with CLDN18-ARHGAP26/6 fusion had a worse survival outcomes (P = 0.03), and got no benefit0 from platinum/fluoropyrimidines based chemotherapy (P = 0.92) compared to fusion-free patients (P = 0.001), which is consistent with the fact of oxaliplatin/fluoropyrimidine resistance acquired in CLDN18-ARHGAP26 introduced gastric cancer cell lines. Overall, this study provides new insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.

  Study EGAS00001002668

• Reconstituting the transcriptome and DNA methylome landscapes of human implantation at single-cell resolution

  Implantation is a milestone event during mammalian embryogenesis. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, the gene regulatory network and epigenetics controlling human embryo implantation remains elusive. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 10,000 single cells at five representative stages of pre/post-implantation development were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm, and trophectoderm lineages, suggesting preparation for the establishment of a mother-to-offspring connection after implantation. Female embryos showed asynchronous progress of dosage loss of X chromosomes during implantation. Furthermore, using the single cell trio-Seq (scTrio-Seq) strategy, re-methylation of the genomes of all the three lineages was unambiguously revealed. Surprisingly, the genome re-methylation of PE lineage were much slower than both EPI and TE lineages during the implantation process, indicating distinct methylome features between EPI and PE although both of which were derived from ICM. Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, informing new insights and future efforts in early embryonic development and reproductive medicine.

  Study EGAS00001003443

• Nanopore_and_Illumina_sequencing_of_human_glioblastomas

  Liquid biopsy analysis refers to methods designed to detect tumour-specific material (e.g., circulating tumour cells or tumour DNA) in body fluids, such as urine or blood samples. A widely-used liquid biopsy approach consists of genotyping the circulating tumour DNA (ctDNA) through sequencing of plasma/serum DNA. Although useful in the context of metastatic disease (where the concentration of ctDNA is high), current liquid biopsy technologies show limited sensitivity of detection for the early detection of cancer, and low specificity, as cancer-related mutations accumulate in healthy tissues as part of the ageing process, thus making it difficult to distinguish these from tumour mutations, and because sequencing errors and true mutations show overlapping profiles. Therefore, developing liquid biopsy protocols with increased sensitivity and specificity represents an urgent clinical need. Here we harness extrachromosomal circular DNA (eccDNA) elements, which are circular DNA structures physically separated from the chromosomes of up to several Mbp long pervasive in human cancers, for liquid biopsy analysis. In this pilot study we will focus on the analysis of glioblastomas, because there is strong evidence for the presence of eccDNA in these tumour types, and because developing liquid biopsy approaches for brain tumours to reduce the invasiveness of brain tumour biopsies remains an unmet clinical need.

  Study EGAS00001005812

• RNA-seq study of human long-term and short-term hematopoietic stem cells from umblical cord blood with lentiviral overexpression of S1PR3

  To investigate the molecular and biological pathways altered by S1PR3OE in human hematopoietic stem cells (HSC), we performed RNA-sequencing (RNA-seq) of LT- and ST-HSC 3 days after transduction with control or S1PR3 overexpression (OE) lentiviral vectors. LT-HSC and ST-HSC from 3 pool of CB lin- were FACS-purified, cells were prestimulated for 4 hours and transduced with lentiviral vectors. At day 3, 2000-5300 BFP+ cells were FACS-purified for RNA isolation with a PicoPure kit. We were able to isolate only 1600-1800 BFP+ cells from LT-HSC control samples as opposed to 4000-5400 BFP+ cells from S1PR3OE samples. Thus, we pooled all control BFP+ LT-HSC cells into one sample for RNA-seq analysis. BFP- LT-HSC from control vector transduction were purified from CB1 as an additional LT-HSC control. Nextera libraries generated from 10 ng RNA from 5 LT-HSC samples (2 controls, 3 S1PR3OE) and 6 ST-HSC samples (3 controls, 3 S1PR3OE) were subjected to 125 bp, paired-end RNA-sequencing on the Illumina HiSeq 2500 with an average of 50 million reads/sample at the Center for Applied Genomics, Sick Kids Hospital.

  Study EGAS00001004798

• Progressive multifocal leukoencephalopathy (PML)

  We generated RNAseq, ATACseq, Multiomics and CITEseq for patients with Progressive multifocal leukoencephalopathy (PML) to profile the chromatin accessibility, transcriptional profiles and surface proteins at single-cell level.

  Study EGAS50000000139

• Human TRIM24-MET fusion HGG RNA-seq

  Human RNA-seq data for TRIM24-MET fusion tumor primary samples and patient/PDOX-derived cell lines. Cells were treated with 0.1% DMSO or EC90 of MET inhibitors (capmatinib, cabozantinib, crizotinib) for 4 hours. BAM files containing aligned (and unaligned) reads to hg19 are provided.

  Dataset EGAD50000000194

• Treatment of genetic screening of hypertriglyceridemia type I, III, and V - HTG Amsterdam

  This is a cohort of patients with extreme hypertriglyceridemia. Patients have been screened for loss of function mutations in LPL, GPIHBP1, APOC2, APOA5 and LMF1.

  Study phs000511

• cfRRBS data plasma healthy donors

  This is cfRRBS data produced from the cfDNA in plasma isolated from healthy, adult donors. Used as a reference for background signal in diseased (onclolytic) plasma cfDNA.

  Study EGAS50000000376

• DAC for "Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis"

  DAC for the data of "Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis" with: • Holger Sültmann • h.sueltmann@dkfz.de • German Cancer Research Center (DKFZ) • Ann-Kathrin Daum • a.daum@dkfz.de • German Cancer Research Center (DKFZ)

  Dac EGAC50000000076

• CITE-seq data of six CK-AML patient samples

  We performed cellular indexing of transcriptomes and epitopes (CITE-seq) of six primary leukemia samples from CK-AML patients. The dataset contains BAM files for each individual sample (D1922 and R0836) or for the hashed pool (HIAML47-HIAML85, P9D-P9R)

  Dataset EGAD50000000633

• Whole genome sequencing raw data for fragile X associated unmethylated expansion carrier 1

  Whole genome sequencing raw data for fragile X associated unmethylated expansion carrier 1. DNA was sequenced using the illumina NovaSeq6000 system. 8x paired end FASTQ files from one DNA sample (UFM 1), 4x R1 files and 4x R2 files.

  Dataset EGAD50000000917

• Whole genome sequencing raw data for fragile X associated unmethylated expansion carrier 2

  Whole genome sequencing raw data for fragile X associated unmethylated expansion carrier 2. DNA was sequenced using the illumina NovaSeq6000 system. 8x paired end FASTQ files from one DNA sample (UFM 2), 4x R1 files and 4x R2 files.

  Dataset EGAD50000000921

• Dataset for "HPV integration induces gene fusions" (Illumina)

  Illumina whole-genome sequencing data for "HPV integration induces gene fusions" We performed short read whole-genome sequencing of five HPV+ head and neck cancer samples using Illumina. The reads are submitted in bam or fastq file format.

  Dataset EGAD50000001305

• Genetic Analysis of Tuberous Sclerosis Complex (TSC) Hypomelanotic Macules

  In this study we searched for mutations in the TSC1 and TSC2 genes in cultured melanocytes from individuals with the genetic disease Tuberous Sclerosis Complex.

  Study phs001236

• Single cell and spatial transcriptomics of adult human adrenal glands

  The data set is composed of single cell transcriptomics data for adrenal glands from 11 deceased organ donors (10x 3') and spatial transcriptomic data for adrenal glands from 4 deceased organ donors (10x Visium).

  Dataset EGAD50000000394

• WGS data for Pancreatic Cancer samples (misc.)

  WGS data for pancreatic cancer samples. These are miscellaneous samples which are part of a tandem duplicator phenotype paper (Farooq et al, NPJ Precision Oncology, 2025). The dataset includes tumour and normal BAM files sequenced on Illumina NovaSeq 6000 and aligned against GRCh38 (n=7 tumour/normal pairs).

  Dataset EGAD50000001833

• Sequencing dataset for the Predictive Endocrine ResistanCe Index (PERCI) in Breast Cancer cases

  Sequencing dataset for the Predictive Endocrine ResistanCe Index (PERCI) in Breast Cancer cases of the WSG-ADAPT trial (NCT01779206). The Oncomine Comprehensive v3 assay (ThermoFisher) and a customized amplicon-based NGS-Panel (DERv2) was performed.

  Dataset EGAD50000001595

• Raw scRNA-seq data for “Characterization of intestinal immune responses in generalized human and murine lipodystrophy”

  Raw 10X 5' v3 scRNA-seq data (GEX) for PBMC of 3 helthy donors and two AGLCD patient timepoints as well as of LPMC of 3 Crohns disease patients and one timepoint of the AGLCD patient.

  Dataset EGAD50000002190

• Raw scTCR-seq data for “Characterization of intestinal immune responses in generalized human and murine lipodystrophy”

  Raw 10X 5' v3 scTCR-seq data (TCR) for PBMC of 3 helthy donors and two AGLCD patient timepoints as well as of LPMC of 3 Crohns disease patients and one timepoint of the AGLCD patient.

  Dataset EGAD50000002191

• Circulating immune cell landscape in colorectal cancer patients

  To understand the circulating immune cells in colorectal cancer patients, we performed single-cell RNA sequencing for 14 PBMC samples from 14 colorectal cancer patients.

  Study EGAS50000000590

• ChIP-seq for 10 samples

  This dataset contains ChIP-seq data generated from two patient-derived xenograft (PDX) models. For each model, sequencing data are provided from input control (n=1), IgG control (n=2), and FOXF1 immunoprecipitation (n=2). All the 10 samples are in bam file type.

  Dataset EGAD50000001786

• Analysis_of_somatic_mutations_in_normal_blood__AML_and_MDS_samples

  Targeted pulldown of genes known to be recurrently mutated in AML & MDS from patient and normal samples using Agilent Sureselect and for some cases also using Illumina Truseq technology.

  Study EGAS00001000525

• Prognostic_factors_in_prostate_cancer__deep_sequencing_pilot_project_TAPG

  This is a pilot project to determine whether the TAPG FFPE DNA’s are suitable for deep sequencing. If successful an investigation of SNP distribution in a larger cohort will follow.

  Study EGAS00001000879