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• Epigenome maps of time-resolved monocyte to macrophage differentiation and innate immune memory

  Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as LPS. We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time dependent manner. ChIP-seq, RNA-seq, WGBS and ATAC-seq data were generated. This analysis identified epigenetic programs in tolerance and trained macrophages, and the potential transcription factors involved. Experimental set-up Time-course in vitro culture of human monocytes. Two innate immune memory states can be induced in culture through an initial exposure of primary human monocytes to either LPS or BG for 24 hours, followed by removal of stimulus and differentiation to macrophages for an additional 5 days. Cells were collected at baseline (day 0), 1 hour, 4 hour, 24 hour and 6 days.

  Dataset EGAD00001002693

• Exome Sequencing Reveals Frequent Inactivating Mutations in BAP1, ARID1A, and PBRM1 in Intrahepatic Cholangiocarcinomas

  Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin remodeling genes (including BAP1, ARID1A, and PBRM1) – mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in genes encoding the metabolic enzymes IDH1 and IDH2 in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These studies highlight the importance of dysregulation of chromatin remodeling in intrahepatic cholangiocarcinomas.

  Study EGAS00001001108

• SCANDARE HNSCC 3' Tag RNA-seq

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 264 FFPE samples at baseline from 90 HNSCC patients using 3'-tag RNA-seq technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001655

• SCANDARE TNBC WES data

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 247 frozen samples at baseline and 138 germline DNA from 139 TNBC patients using WES technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001661

• SCANDARE TNBC WGS data

  SCANDARE (NCT03017573) is a multicentric biobanking study, enrolling adult patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), triple negative breast cancer (TNBC), ovarian and cervical cancer. Tumor tissue and blood samples are collected at several time points during patient's journey, including at diagnosis, post-neoadjuvant chemotherapy in case of neoadjuvant treatment, at surgery, at recurrence and at disease progression following treatment initiated at recurrence. Since its launch in 2017 at Institut Curie, SCANDARE has enabled the longitudinal collection and preservation of samples for in-depth analyses. Here, we describe molecular alterations in 108 FFPE samples at baseline and 108 germline DNA from 108 TNBC patients using WGS technology, with FASTQ files deposited in the dataset.

  Dataset EGAD50000001662

• Full blood mRNA sequencing of myotonic dystrophy type 1 patients after cognitive behavioural therapy

  This dataset consists of 60 mRNA sequencing runs from full blood of 31 myotonic dystrophy type 1 patients, of which for 27 patients reliable data is available before and after 10 months of cognitive behavioural therapy. >30 million 150 bp paired end reads were obtained with UMI-labeled adapters to facilitate filtering of PCR duplicates. Via UMI-analysis we found samples with the aliases sample_01 and sample_02 to contain a very high number of PCR duplicates and recommend the use of these samples only with highest caution or not at all.

  Dataset EGAD00001008383

• Dataset for negative_WGS

  WES/WGS sequencing data of 239 chromothriptic tumor and control runs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001009279

• Unravelling the contribution of HIF pathway and its therapeutic potential in human AML leukemia-initiating cells

  We performed single cell RNA sequencing (scRNA-seq) from bone marrow on 11 pediatric (0-14 years-old) and adolescent and young adult (AYA) (15-39 years-old) de novo AML samples (Dx) (4 inv(16), 3 t(8;21) and 4 rMLL). In addition, for some patients also relapse sample was sequenced (2 inv(16), 2 t(8;21) and 3 rMLL). Cells were sorted into CD34+/CD38- and CD34-/CD38+ and sequenced separately.

  Dataset EGAD00001008514

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  Study EGAS00001008448

• The Genetic and Transcriptomic Evolution of Melanoma

  The overarching goal of the study was to better understand the evolution of melanoma. To do this, we collected archival tissue of melanomas adjacent to their intact, remnant precursor lesions. We also collected archival tissue of primary melanomas and their matching metastases. From the formalin-fixed paraffin-embedded (FFPE) blocks, we microdissected non-neoplastic (normal), precursor, and descendent portions of tissue. Both RNA and DNA were extracted from the microdissected tissues and subjected to next generation sequencing. In summary, we performed matched DNA/RNA sequencing of melanoma/precursor/normal trios, allowing us to trace the genetic and transcriptomic evolution of melanoma.

  Study phs001550

• Understanding population genetics and patterns of genome-wide heterozygosity in a sample of the Croatian isolated populations (ESGIDalmatians)

  Using high-throughput sequencing technologies and analytical tools, we conduct an exome sequencing study that will help understand the population genetics of a Croatian island isolate, in a sample of 200 subjects from the Adriatic island of Vis who were selected to reflect islanders with at least four known ancestors in grandparental line who are original islanders.

  Dataset EGAD00001001387

• STAT1 AM RNAseq

  The transcriptome of peripheral blood cells (PBMCs) from control or patients with an activation mutation on the STAT1 gene was analyzed. This analysis aimed to identify the major changes in the circulating immune cells of patients with STAT1 mutation and compare this with the result of the perturbation prediction tool huva (human variation, R).

  Dataset EGAD00001006962

• Somatic mutation and selection at epidemiological scale - Sanger_NanoSeq_RandD

  Bottleneck sequencing of human tissue including neurons, cord blood, sperm This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/. As we age, many tissues become colonised by microscopic clones carrying somatic driver mutations. Some of these clones represent a first step towards cancer whereas others may contribute to ageing and other diseases. However, our understanding of the clonal landscapes of human tissues, and their impact on cancer risk, ageing and disease, remains limited due to the challenge of detecting somatic mutations present in small numbers of cells. Here, we introduce a new version of nanorate sequencing (NanoSeq), a duplex sequencing method with error rates of less than 5 per billion base pairs, which is compatible with whole-exome and targeted gene sequencing. Deep sequencing of polyclonal samples with single-molecule sensitivity enables the simultaneous detection of mutations in large numbers of clones, yielding accurate somatic mutation rates, mutational signatures and driver mutation frequencies in any tissue. Applying targeted NanoSeq to 1,042 non-invasive samples of oral epithelium and 371 samples of blood from a twin cohort, we found an unprecedentedly rich landscape of selection, with 46 genes under positive selection driving clonal expansions in the oral epithelium, over 62,000 driver mutations, and evidence of negative selection in some genes. The high number of positively selected mutations in multiple genes provides high-resolution maps of selection across coding and non-coding sites, a form of in vivo saturation mutagenesis. Multivariate regression models enable mutational epidemiology studies on how carcinogenic exposures and cancer risk factors, such as age, tobacco or alcohol, alter the acquisition and selection of somatic mutations. Accurate single-molecule sequencing has the potential to unveil the polyclonal landscape of any tissue, providing a powerful tool to study early carcinogenesis, cancer prevention and the role of somatic mutations in ageing and disease.

  Dataset EGAD00001015624

• STARR-seq of ERa binding sites in MCF7 and Ishikawa cell lines

  A oligo-captured STARR-seq library was generated using as targets ERa binding regions indetified by ChIP-seq in Ishikawa (Endometrial cancer) and T47D (breast cancer) cell lines and, breast cancer primary tissues. STARR-seq assays have been performed in MCF-7 and Ishikawa cell lines. Cells have been cultured for 3 days in hormone deprivated (phenol-red free) media and stimulated for 6 hours by 10nM estradiol (E2) or DMSO (negative control).

  Dataset EGAD50000000015

• Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___WGS

  The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.

  Study EGAS00001003012

• Analysis of MPNST progression at single-cell resolution

  Malignant Peripheral Nerve Sheath Tumors (MPNST) are soft-tissue sarcomas with poor prognosis and a lack of treatment options. About half of them arise in people with Neurofibromatosis Type 1 (NF1). In this study, we set out to explore the malignant progression and tumor heterogeneity by exploring the different tumors along the MPNST progression at the single cell level. This work is part of the project "NF1-Associated Peripheral Nerve Sheath Tumors at Single-Cell Resolution: Heterogeneity, Tumor Growth, and Malignant Progression".

  Study EGAS50000001747

• Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___UGI___WGS

  The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.

  Study EGAS00001003541

• Exome_Sequencing__to_Identify_Causes_of_Leukaemia_Predisposing_Congenital_Neutropenias

  The objective of this study is to identify the causative genes in two unrelated congenital neutropenia families. We aim to whole exome sequence the affected individuals, unaffected siblings and parents in both cases in an effort to idenitfy the causative genetic mutation. Exome capture will be performed using Agilent SureSelect system. Subsequently, exome libraries will sequenced using the Illumina HiSeq platform. Sequence variant calling will be done in house and common variants excluded using public databases and data from unaffected family members.

  Study EGAS00001000100

• Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___GI___TPS___WGS

  The aim of this project is to investigate somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the gastrointestinal tract. The project will involve the study of normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to identify and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.

  Study EGAS00001003089

• Exploring_the_landscape_of_somatic_mutations_in_normal_tissue___BD___WGS

  The aim of this project is to investiagte somatic mutations, including rates of mutations and signatures, and clonal dynamics in normal (non-cancerous) human tissues from the biliary tree. The project will involve the studyof normal tissues from healthy individuals and those with specific candidate diseases. We are utilising laser capture microscopy to idnetifiy and isolate specific cell populations which are then subjected to whole genome sequencing to estimate mutational burdens and begin to understand clonal structures across the normal tissues.

  Study EGAS00001003014

• Differentiation-associated ISG expression of NK cells in chronic viral hepatitis

  Little is known about the effects of ISGs on NK cell responses in chronic viral hepatitis. Here, we determined the expression, regulation and function of ISGs in NK cells with respect to phenotype and function, we performed high-throughput single cell RNA sequencing of circulating CD3-CD56+ NK cells from healthy donors (HD) and patients with chronic HBV or HCV infections.

  Study EGAS00001007771

• Constrained hypermutation and absence of TERT promoter mutations in Lynch syndrome-associated urothelial cancer

  Lynch syndrome is a hereditary condition characterized by defective DNA mismatch repair and high incidence of several cancers, including urothelial cancers (UC) of the upper urinary tract and bladder. We set out to study the somatic landscape of LS-associated urothelial cancer (LS-UC) by analyzing 41 surgical tumor samples and 3 urine DNA samples from 34 LS-UC patients.

  Study EGAS50000000831

• Inherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells

  Cellular DNA damage caused by reactive oxygen species is repaired by the base excision repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. However, the mechanistic progression from germline MUTYH mutations to MUTYH-Associated Polyposis (MAP) is incompletely understood. Here, we sequenced normal cell DNAs from 10 individuals with MAP and study the somatic mutation burden and mutational signatures.

  Dataset EGAD00001007958

• INSIGHT: VHL Case Report

  The overall goal of this study is to uncover contributors to inherited cancer through analysis of individuals and families with, or at risk of, a hereditary cancer syndrome. In addition, we hope to elucidate novel mechanisms of tumourigenesis in hereditary cancer patients. This specific report highlights a rare case of VHL mosaicism and shows the value of tissue testing in VHL variant negative cases.

  Study EGAS00001005895

• Whole-exome sequencing of intravascular large B-Cell lymphoma

  Intravascular large B-cell lymphoma (IVLBCL) is a unique form of diffuse large B-cell lymphoma (DLBCL) characterized by extranodal cell growth especially in small vessels without systemic lymphadenopathy. The limitation in obtaining sufficient tumor materials hampers understanding the molecular pathogenesis of IVLBCL. We performed whole-exome sequencing of IVLBCL using plasma-derived cell-free DNA (cfDNA) and patient-derived xenograft (PDX) samples.

  Study EGAS00001003970