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• Single cell transcriptomic and genomic profiling of carcinogenesis in patients with familial adenomatous polyposis

  Familial Adenomatous Polyposis (FAP) is characterized by hundreds to thousands of adenocarcinomas at different evolutional stages in the colon and rectum. Much effort has been made to illuminate the key genomic alterations that facilitate the transition from adenoma to carcinoma. However, the strong heterogeneity of the tumors may hamper these efforts. Here, by sequencing matched adjacent normal tissues, adenomas at different stages and carcinomas from the same patient, we precisely traced the process of colorectal carcinogenesis. Our study offers an accurate genomic landscape during the initiation and progression of carcinogenesis, especially for the transition between adenomas and carcinomas.

  Study EGAS00001003598

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

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

  Study EGAS00001003748

• scRNAseq and scATACseq of placebo controlled-trial on MMR non-specific effects

  The project includes sequencing data of isolated PBMCs extracted from donors that received the MMR vaccine and donors that received placebo, both containg samples before and after the vaccine. In total, 6 MMR-vaccinated and 6 Placebo donors for both timepoints were included in the scRNAseq data. In total, 12 MMR-vaccinated and 12 Placebo donors for both timepoints were included in the scATACseq data. The main goal of the project is studying the non-specific effects of the vaccine and its possible use as an inducer of trained immunity in vivo.

  Study EGAS00001006787

• RNA sequencing data of 142 samples from 142 patients with HER2+ breast cancer treated with letrozole or tamoxifen (SOLTI PAMELA trial)

  PAMELA (NCT01973660) is a non-randomized, open-label, multicentric, prospective translational research study in stage I-IIIA HER2+ breast cancer designed to evaluate the ability of the PAM50 intrinsic subtypes to predict pCR in the breast (pCRB) following 18 weeks of neoadjuvant lapatinib and trastuzumab (+/- hormonal therapy if hormone receptor [HR] positive). Patients with HR+ disease received letrozole (if postmenopausal) or tamoxifen (if pre-menopausal). The primary objective was to compare the pCRB rates of the HER2-E versus the non-HER2-E subtypes in the intent-to-treat population.

  Study EGAS00001006410

• Breast Cancer - Very young women

  This project will focus on sequencing of breast cancer from young age cancer patients characterized by age at diagnosis under 35. Based on the incidence rate by Korean National Cancer Incidence Database, breast cancer is the most common solid tumors among young adults aged 15-34 excepting thyroid cancer (Cancer statistics in Korea (2012)). This project just started from the mid of 2015. National cancer center in Korea are collecting more than 100 tumor specimens from breast cancer patients aged 20-34. Genetic features of young patients will be investigated with somatic mutation pattern, structural variations, and canonical pathways.

  Study EGAS00001001908

• Identification_of_drug_resistance_genes_in_cancer_cell_lines_by_insertional_mutagenesis

  Our aim is to identify genes involved in resistance to anti-cancer therapies. In order to do this we have taken advantage of a lentiviral vector (LV)-based insertional mutagen to mutagenize cancer cell lines. LV-transduced cell lines were then treated with anti-cancer therapies and the emergence of resistant clones scored. DNA from pools of resistant clones was collected, subjected to custom capture by baits designed against the LV sequence, and then sequenced to identify the LV-genomic junction. We hope that the identification of recurrently targeted genes in resistant cell population will allow us to identify genes that mediate drug resistance.

  Study EGAS00001001035

• Methylation_changes_in_OA_patients_with_chronic_exposure_to_cobalt_and_chromium

  We have whole blood from a population of 70 patients, half exposed chronically to an excessof metals cobalt and chromium. The 2 groups are age, sex, and OA diagnosis matched. The2 groups have systemic differences in bone mass and turnover, and other systemicdifferences.We will type the cohort of 70 individuals on the Illumina 450k methylation array and willcompare between the two groups.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/

  Study EGAS00001001180

• 503 genotypes from Inner Asia used in 'Close inbreeding and low genetic diversity in Inner Asian human populations despite geographical exogamy' publication

  Inner Asia is particularly interesting to understand human history and evolution, as two groups presenting contrasting cultural traits (notably their language, their social organisation and matrimonial system) cohabit. We sampled 503 individuals from these two groups, belonging to 17 populations from 11 distinct ethnic groups (AltaiKizhi, Kazakh, Khakas, Kyrgyz, Mongolian, Shore, Tajik, Telengit, Tubalar, Turkmen and Uzbek). The samples were then genotyped with 5 different DNA-arrays and, after quality-control, the 253,532 autosomal SNPs present in all the arrays were merged together in the present dataset.

  Study EGAS00001002951

• HipSci___RNAseq___Rare_BBS

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNAseq on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome 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/

  Study EGAS00001001318

• Chracterising_cellur_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells

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

  Study EGAS00001002599

• Ibrutinib induces a global chromatin reorganisation in chronic lymphocytic leukaemia

  Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in developed countries. Ibrutinib (PCI-32765), a specific and irreversible inhibitor of Bruton's Tyrosine Kinase (BTK) represents a major step forward in the treatment of CLL. We have undertaken a detailed analysis of the changes happening to the chromatin structure in CLL cells from patients continuously receiving oral doses of ibrutinib. ChIP-seq has been performed for H3K4me3, H3K27ac, H3K27me3 and EZH2 . We observed that Ibrutinib-dependent lymphocytosis correlates with a global and transient recruitment of EZH2 to active cis-regulatory elements and increased H3K27me3.

  Study EGAS00001002827

• Preferential infiltration of distinct Vγ9δ2 T cells into Glioblastoma multiforme

  Glioblastoma multiforme (GBM), the most fatal CNS cancer, is highly infiltrative as a result of phenotypic alteration of cancer cells mainly driven by a mutual interaction among cancer cells, tumor-associated macrophages (TAMs) and other stromal cells. This work aims at characterizing GBM-infiltrating γδ T cells that may regulate the GBM tumor microenvironment and cancer cell gene expression. V(D)J repertoires of tumor-infiltrating and blood circulating γδ T cells from 4 patients were analyzed by NGS-based TCR sequencing. RNA gene expression profiling and immunostaining of cancer tissues were performed as well.

  Study EGAS00001002790

• Fetal hemoglobin in sickle cell disease patients from Tanzania

  Levels of fetal hemoglobin have been associated with differences in severity and outcome of sickle cell disease (SCD). While some genetic associations have been reported between SNPs and HbF level, little of the variance in the trait is explained, and most studies have focused on African American, rather than African samples. We have carried out a GWAS in a collection of SCD patients from Dar es Salaam, Tanzania. This sample represents a diverse, metropolitan collection of individuals from East Africa. Omni 2.5M genotypes and HbF levels (measured after 5 years of age) are available.

  Study EGAS00001000990

• Congenital_anosmia_1

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). To date, only a single recessive gene underlying complete anosmia has been identified. Here we sequenced the exomes of 10 individuals from a single family, including three with complete anosmia, across three generations to identify the genetic basis of congenital anosmia in this family. 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/

  Study EGAS00001001124

• HipSci___RNAseq___Rare_Monogenic Diabetese

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNAseq on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Monogenic Diabetes. 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/

  Study EGAS00001001137

• Single-cell RNA-sequencing reveals that glioblastoma recapitulates a normal neurodevetlopmental hierarchy

  We discovered a conserved neural tri- lineage cancer hierarchy centered around glial progenitor-like cells. We also found that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.

  Study EGAS00001004422

• Understand_Paratyphoid_Disease___host_responses_to_human_challenge_with_S__Paratyphi_A

  This project aims to evaluate the transcriptional response to disease measured in whole blood of participants who developed enteric fever after challenge and, importantly, those who were challenged but stayed well throughout the challenge period. This data will provide unique coverage of the transcriptome and will yield invaluable insight after integration with a wealth of clinical data collected during this trial. 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/

  Study EGAS00001001260

• Whole Genome Sequencing of 317 individuals from the Pacific region

  Although genetic studies of modern Oceanians have revealed varying levels of admixture with populations of East Asian ancestry, attributed to the Austronesian expansion, the early peopling history of Oceania remains poorly characterized. Additionally, it is currently unknown whether and how the settlement of the Pacific was accompanied by genetic adaptation to island environments, and if archaic introgression facilitated this process in Oceanians, who present the highest worldwide levels of combined Neanderthal and Denisovan ancestry. This study reports the first whole genome-based survey that addresses a wide range of questions related to the demographic and adaptive history of Pacific populations.

  Study EGAS00001004540

• Single cell T cell Landscape and T Cell Receptor Repertoire Profiling of AML in Context of PD-1 Blockade Therapy

  Eight pretreatment and 14 posttreatment bone marrow (BM) aspirates from 8 patients with R/R AML treated with azacitidine and nivolumab along with 2 control BM from healthy donors were profiled with scRNA sequencing with matching scTCR -, scBCR - and scATAC sequencing. Additionally, the targeted DNA sequencing in at least 1 time point per patient (total evaluated 17/22 samples, two samples were performed using CLIA-certified molecular diagnostic assay and data is not available) was performed. The Fastq files and/or bam files are available in this dataset.

  Study EGAS00001004894

• Ultraviolet radiation drives mutations in a subset of mucosal melanomas

  Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We present the largest cohort of mucosal melanomas of conjunctival origin to be analyzed by whole genome sequencing and show a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset could benefit from treatments currently used for common cutaneous melanoma.

  Study EGAS00001004697

• Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies

  To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). Laser capture microdissection of tumour islets was performed on samples prior to chemotherapy, after three cycles of chemotherapy and at recurrence. Long frament read whole genome sequencing was performed and mutations were identified. To our knowledge, this is the first longitudinal study that attempts to investigate spatial and temporal micro-heterogeneity in cancer.

  Study EGAS00001001909

• Transcriptome profiling of human plucked frontal and occipital hair follicles

  Androgenetic alopecia (AGA) is characterized by a progressive and androgen-dependent loss of hair from the frontal and vertex regions of the scalp. Although large-scale genetic analyses have identified >300 genetic risk factors, the underlying causal genes and pathways, and their involvement in core pathophysiological mechanisms, remain unclear. In the present study, systematic profiling of differential mRNA and microRNA expression was performed in human hair follicle samples from frontal and occipital scalp regions. Taken together, the present data improve understanding of the genomic regions, genes, and pathways that are implicated in AGA pathobiology.

  Study EGAS00001002832

• Exploring_the_heterogeneity_of_sarcoma_using_single_cell_sequencing_

  Multi region samples are collected from patients, with consent, immediately after resection of the tumour. Samples are digested and sorted using FACS as single cells into lysis buffer. Cells are then stored until further processing for G&T-seq. After sequencing, we will explore intra-tumour heterogeneity using computational approaches to integrate RNA and DNA data onto the tumour phylogeny 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/

  Study EGAS00001002866

• Identification of hypermutation and defective mismatch repair in ctDNA from metastatic prostate cancer

  DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer. Furthermore, since hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools. We analyzed cell-free DNA targeted sequencing data from 434 metastatic prostate cancer patients with circulating tumor DNA (ctDNA) purity above 2%. Samples with somatic hypermutation were subjected to 150x whole exome sequencing. These data allowed us to interrogate the salient genomic properties of this rare prostate cancer subtype and correlate findings with patient clinical outcomes.

  Study EGAS00001003899

• Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities

  Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data, we applied non-negative matrix factorization, which identified four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed signature (SCLC-A, N, P and I, respectively). The presence of these subtypes were then validated in tumor gene expression data from the IMpower133 clinical trial.

  Study EGAS00001004888