22959 results for "ega"

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• RNA-seq data from 164 advanced prostate tumors generated by the West Coast Dream Team including 42 paired samles

  164 pairs of FASTQ files from metastatic Castration-Resistant Prostate Cancer (mCRPC) sequenced on HiSeq 4000 instruments. Patients were enrolled in the West Coast Dream Team study. Biopsies include various tissue sites including bone, soft tissue, and lymph node. 42 pairs prior to enzalutamide treatment and at progression from 21 patients are included.

  Dataset EGAD00001009065

• Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

  Background: The disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative of aggressive tumor behaviour and can thereby complement the prognostically favorable 1p/19q co-deletion. Results: Genome-wide, 50 base pair single-end, sequencing was performed to detect CNAs in a clinically well-characterized cohort of 98 formalin-fixed paraffin-embedded low-grade gliomas. CNAs are correlated with overall survival as an endpoint. Seventy-five additional samples from spatially distinct regions and paired recurrent tumors of the discovery cohort were analysed to interrogate the intratumoral heterogeneity and spatial evolution. Loss of 10q25.2-qter is a frequent subclonal event and significantly correlates with an unfavorable prognosis. A significant correlation is furthermore observed in a validation set of 126 and confirmation set of 184 patients. Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/ 19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors. Conclusions: CNAs in low-grade gliomas display extensive intratumoral heterogeneity. Distal loss of 10q is a late onset event and a marker for reduced overall survival in low-grade glioma patients. Intratumoral heterogeneity and higher frequencies of distal 10q loss in recurrences suggest this event is involved in outgrowth to the recurrent tumor.

  Dataset EGAD00001001000

• Transcriptome human nasal epithelium

  1. Odors are detected, firstly, by olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose. This neurons then project directly to the olfactory bulb in the brain. Olfaction depends on cellular regeneration of the OE, olfactory bulb and hippocampus, and on their continual re-wiring. The olfactory neural pathway includes regions of the frontal, temporal and limbic brain, which in turn overlap with brain areas involved in brain disorders. OSNs are the only aspect of the human brain exposed to the external environment. This not only makes them vulnerable to environmental changes, but also accessible for biomedical studies. We have already sequenced and developed a protocol for analyzing the transcriptome of mouse main olfactory epithelium and single OSNs. We propose here to perform a similar study for samples from the human olfactory epithelium. We have developed a minimally invasive method for obtaining human OSNs, among other cells from the nasal epithelium. In this experiment, we have obtained cell samples from the olfactory epithelium, including OSN, from healthy volunteers. We would like to further characterize them by RNA sequencing. This will give us valuable insight into human olfaction. It will also provide a first step into a new avenue to study, and find biomarkers for, brain diseases though the analysis of these easily available neurons. 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/

  Dataset EGAD00001002226

• Influence of the Microbiome on Epigenetic Mechanisms in IBD

  Live CD4 T cells were sorted from inflamed and non-inflamed tissue samples of IBD patients or from healthy and IBD blood samples. ATAC-Seq libraries were generated from live CD4 T cells sorted from i) inflamed and non-inflamed tissue samples, ii) healthy and IBD blood samples, or from iii) CD4 T cell subsets polarised from healthy blood samples. After isolating crude nuclei, 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. On the other hand, single cell RNA-Seq libraries were generated exclusively from inflamed and non-inflamed tissue samples of Crohn’s disease patients. Briefly, live CD4 T cells were captured and encapsulated before cDNA amplification using the 10X Genomics Chromium Platform. Samples were prepared as outlined by 10x genomics Single Cell 3’ Reagent Kits v2 user guide. Samples were sequenced on a HiSeq 2500 with the following run parameters: Read 1 – 26 cycles, read 2 – 98 cycles, index 1 – 8 cycles.

  Dataset EGAD00001011066

• Activation of Wnt/β-catenin signalling by mutually exclusive FBXW11 and CTNNB1 hotspot mutations drives salivary gland basal cell adenoma - WES

  Wnt signalling must be 'just right' to promote tumour growth. Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours that can be difficult to distinguish from each other and other salivary gland tumour subtypes. Due to their rarity, the genomic profiles of BCA and BCAC have not been explored. Using whole-exome and transcriptome sequencing of BCA and BCAC cohorts, we identify a novel recurrent FBXW11 missense mutation (p.F517S) in BCA, that was mutually exclusive with the previously reported CTNNB1 p.I35T gain-of-functon (GoF) mutation. These driver events collectively accounted for 94% of BCAs. In vitro, mutant FBXW11 had a dominant negative affect, characterised by defective binding to β-catenin and the accumulation of β-catenin in cells. This was consistent with the nuclear expression of β-catenin observed in BCA cases harbouring the FBXW11 p.F517S mutation and activation of the Wnt/β-catenin pathway and defines a novel mechanism of Wnt pathway control. The genomic profiles of BCAC were distinct from BCA, with hotspot DICER1 and HRAS mutations and putative driver mutations affecting PI3K/AKT and NF-κB signalling pathway genes. A single BCAC, which may represent a malignant transformation of BCA, harboured the recurrent FBXW11 mutation. These findings have important implications for the diagnosis and treatment of BCA and BCAC, which, despite histopathologic overlap, may be unrelated entities.

  Dataset EGAD00001015365

• The earliest stages of neoplastic transformation in Familial Adenomatous Polyposis

  The succession of somatic genetic events associated with the conversion of a normal colorectal epithelial cell into a colorectal carcinoma constitutes a paradigmatic model of cancer development. Familial Adenomatous Polyposis (FAP) is caused by constitutional inactivating mutations in APC, the central gatekeeper gene of colorectal cancer, and is associated with a substantially increased lifetime-risk of colorectal cancer. To investigate the earliest stages of neoplastic change due to APC inactivation, we microdissected and individually whole genome sequenced 279 histologically normal and abnormal colorectal crypts from 15 individuals with FAP. Histologically normal crypts generally exhibited similar mutation burdens and mutational signatures to normal crypts from wild-type individuals of the same age, with 1/110 carrying a somatic inactivating APC mutation. By contrast, 9/18 aberrant crypt foci carried somatic APC mutations and exhibited modestly increased burdens of some mutational signatures found in normal crypts. 12/13 diminutive adenomatous polyps (less than 5mm diameter) showed somatic APC mutations and carried substantially increased mutation loads of most mutational signatures present in normal crypts. Phylogenetic trees of crypts from aberrant crypt foci and adenomatous polyps revealed that some had acquired their initiating somatic APC mutations decades previously during the first few years of life. The results catalogue the changes in somatic mutation rates, mutational processes and “driver” mutations in cancer genes during the earliest stages of colorectal neoplastic transformation initiated by APC inactivation and highlight the long periods of clonal evolution required for a cancer to develop.

  Dataset EGAD00001015477

• The earliest stages of neoplastic transformation in Familial Adenomatous Polyposis

  The succession of somatic genetic events associated with the conversion of a normal colorectal epithelial cell into a colorectal carcinoma constitutes a paradigmatic model of cancer development. Familial Adenomatous Polyposis (FAP) is caused by constitutional inactivating mutations in APC, the central gatekeeper gene of colorectal cancer, and is associated with a substantially increased lifetime-risk of colorectal cancer. To investigate the earliest stages of neoplastic change due to APC inactivation, we microdissected and individually whole genome sequenced 279 histologically normal and abnormal colorectal crypts from 15 individuals with FAP. Histologically normal crypts generally exhibited similar mutation burdens and mutational signatures to normal crypts from wild-type individuals of the same age, with 1/110 carrying a somatic inactivating APC mutation. By contrast, 9/18 aberrant crypt foci carried somatic APC mutations and exhibited modestly increased burdens of some mutational signatures found in normal crypts. 12/13 diminutive adenomatous polyps (less than 5mm diameter) showed somatic APC mutations and carried substantially increased mutation loads of most mutational signatures present in normal crypts. Phylogenetic trees of crypts from aberrant crypt foci and adenomatous polyps revealed that some had acquired their initiating somatic APC mutations decades previously during the first few years of life. The results catalogue the changes in somatic mutation rates, mutational processes and “driver” mutations in cancer genes during the earliest stages of colorectal neoplastic transformation initiated by APC inactivation and highlight the long periods of clonal evolution required for a cancer to develop.

  Dataset EGAD00001015471

• Genome wide association study of Coeliac Disease

  We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression

  Study EGAS00000000057

• A Comprehensive Catalogue of Somatic Mutations from a Human Cancer Genome

  We have carried out complete sequencing of the genome of the human male maligant melanoma cell line COLO-829 using the Illumina Genome Analyzer II. We generated a sequencing library with a median insert size of ~200 bp following random fragmentation and gel fractionation of the genomic DNA. We sequenced 75 bases from both ends of these templates to cover the COLO-829 genome to an average depth of more than 40x. We have carried out purity-filtering (PF) to remove mixed reads, where two or more different template molecules are close enough on the surface of the flow-cell to form a mixed or overlapping cluster. No other filtering of the data has been carried out prior to submission. We have also submitted sequence data for a lymphoblastoid control cell line COLO-829BL from the same individual.

  Study EGAS00000000052

• Massive Genomic Rearrangment Acquired in a Single Catastrophic Event During Cancer Development

  Cancer is driven by mutation. Using Agilent exome hybridisation capture and Illumina GA massively parallel sequencing technology, we aim to sequence ~1600 microRNAs plus the protein coding genome of 25 matched human renal cancer samples. Bespoke algorithms are being developed to identify the somatically acquired point mutations, insertions and deletions in these samples. This project will give unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with renal cancer development.Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 25 renal cancers and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 50 exome libraries and mapped to build 37 of the human reference genome to facilitate the identification of novel cancer genes.

  Study EGAS00000000029