11795 results for "cancer rna-seq"

in 19.64 milliseconds.

• scRNA-seq, scTCR-seq and scBCR-seq of 21 individuals post Covid'19 vaccination.

  This data includes scRNA-seq, scTCR-seq and scBCR-seq of 21 individuals post Covid'19 vaccination. Individuals range from the ages 52 to 75. Samples were genotype multiplexed in an overlapping mixture design, pooled, and sequenced on 16 lanes (10X, 5' GEM).

  Dataset EGAD00001011201

• HCA Female Reproductive Adult WSSS RNA

  HCA Endometrium_LM The endometrium regenerates monthly and its transformation is executed through dynamic changes in states and interactions of multiple cell types. Using transcriptomics methods we seek to profile changes of the endometrium across the menstrual cycle. Our map will have implications in women's health and cancer, by enabling the interpretation of GWAS analyses or the studying functional consequences of somatic mutations. 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 EGAD00001007909

• Raw molecular data for "Subclonal immune evasion in non-small cell lung cancer"

  Whole exome, RNA sequencing and TCR sequencing of organoid samples derived from TRACERx patients. The dataset also includes whole exome sequencing from the tumour samples from which the organoids were generated, as well as whole exome sequencing from PDX derived from said tumours.

  Dataset EGAD00001015537

• Genetic control of the transcriptomic response of monocytes to bacterial and viral stimuli assessed by RNA-seq in Africans and Europeans

  Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses, and their genetic and evolutionary determinants, remain undefined. Here, we characterized, using RNA-sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli - ligands activating Toll-like receptors pathways (TLR1/2, TLR4 and TLR7/8) and influenza virus - and mapped expression quantitative trait loci (eQTL). We identify multiple cis- and trans-eQTL that contribute to the marked differences in immune responses detected within and between populations, including a TLR1 master regulator that decreases expression of pro-inflammatory genes in Europeans only. We show that regulatory variants have been privileged targets of natural selection, uncovering evolutionarily advantageous mechanisms, such as attenuated inflammation. Finally, we demonstrate that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges, and identify archaic haplotypes that contributed to population genetic adaptation.

  Study EGAS00001001895

• Single-cell RNA-seq of celiac disease-specific plasma cells

  Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGP) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls, and performed RNA-sequencing with clonal inference and transcriptomic analysis of 3251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy-chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific vs non-disease-specific PCs and between short-lived vs long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term-treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.

  Study EGAS00001004623

• Genomic Advances in Sepsis (GAinS): RNA-seq

  Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 34 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected on the first, third and/or fifth day following ICU admission. RNA was extracted from leukocytes isolated at the bedside using LeukoLOCK kits. We have previously identified sepsis response signatures (SRSs), transcriptomic endotypes that are associated with differential early mortality (Davenport et al, Lancet Respir Med, 2016; Burnham et al, AJRCCM, 2017) and response to treatment in a clinical trial (Antcliffe et al, AJRCCM, 2018). We generated RNA sequencing data on 903 samples, including 134 samples repeated from our previously released microarray data. Libraries were prepared using NEB Ultra II Library Prep kits (Illumina) and sequenced on a NovaSeq 6000. Reads were aligned to the reference genome (GRCh38) using STAR and gene counts quantified using featureCounts (annotation Ensembl v99). Counts were TMM-normalised and log-transformed. Following QC, processed data were available on 864 samples from 667 unique patients.

  Dataset EGAD00001008730

• ChIP-Seq of TFEB in LT-HSC

  ChIP-Seq of TFEB in LT-HSC

  Study EGAS00001005462

• Targeted sequencing of genes recurrently mutated in AML

  Background Massively parallel sequencing technology has transformed cancer genomics. It is now feasible, in a clinically relevant time-frame, for a clinically manageable cost, to screen DNA from patient tumours for mutations essentially genome-wide. The challenge for personalised medicine will be to increase the sample size to thousands or tens of thousands of well-characterised cases in order to attain sufficient statistical power to stratify patients accurately across the complexity and genomic heterogeneity expected for most of the common tumour types. Currently, whole genome sequencing on this scale is not feasible, and targeted sequencing of relevant portions of the genome will be required. Pilot data We have developed protocols for large-scale, multiplexed sequencing of 100-200 genes in thousands of samples. Essentially, using robotic technology, genomic DNA from the cancer specimen is processed into sequencing libraries with unique DNA barcodes, thereby allowing sequencing reads to be attributed to the sample they derive from. Currently, these sequencing libraries can be generated in a 96-well format using fully automated protocols, and we are exploring methods to expand this to a 384-well format. The sequencing libraries are pooled and hybridized to custom sets of RNA baits representing the genomic regions of interest. Sequencing of the pulled-down libraries is done in pools of 48-96 samples per lane of an Illumina Hi-Seq. This protocol is already implemented at the Sanger Institute. We have published proof that somatic mutations in novel cancer genes can be identified from exome-wide sequencing. In unpublished pilot data, we have established the feasibility of robotic library production, custom pull-down, and multiplexed sequencing of barcoded libraries for 100 known myeloid cancer genes across 760 myelodysplasia samples. Highlights of the data thus far analysed reveal that the coverage is remarkably even between samples; when 96 samples are run, average coverage per lane of sequencing is ~250, with 90-95% of targeted exons covered by >25 reads; known mutations can be discovered in the data set; and the protocol is amenable to whole genome amplified DNA. The bioinformatic algorithms for identification of substitutions and indels in pull-down data are well-established; we have pilot data proving that copy number changes, LOH and genomic rearrangements in specific regions of interest can also be identified by tiling of baits across the relevant loci. Proposal We propose to apply this methodology to 10000 samples from patients with AML enrolled in clinical trials over the last 10-20 years. Oncogenic point mutations and potentially genomic rearrangements will be identified, and linked to clinical outcome data, with a view to undertaking the following sorts of analyses: ? Identification of co-occurrence, mutual exclusivity and clusters of driver mutations. ? Correlation of prognosis with driver mutations and potentially gene-gene interactions ? Exploration of genomic markers of drug response Ultimately, we would like to be in a position to release the mutation data together with matched clinical outcome data to genuine medical researchers via a controlled access approach, possibly within the COSMIC framework (www.sanger.ac.uk/genetics/CGP/cosmic/). The vision here is to generate a portal whereby a clinician faced with an AML patient and his / her mutational profile can obtain a ?personalised? prediction of outcome, together with a fair assessment of the uncertainty of the estimate. With a sufficient sample size, there would also be the potential to develop decision support algorithms for therapeutic choices based on such data.

  Dataset EGAD00001000606

• Mapping Systemic Lupus Erythematosus Heterogeneity at the Single Cell Level

  Patients with Systemic Lupus Erythematosus (SLE) display a complex blood transcriptome whose cellular origin is poorly resolved. Using single-cell RNA-seq, we profiled ~276,000 PBMCs from 33 children with SLE (cSLE) with different degrees of disease activity (DA) and 11 matched controls. Increased expression of Interferon-stimulated genes (ISGs) distinguished cSLE from healthy control cells. The high-ISG expression signature (ISGhi) derived from a small number of transcriptionally defined subpopulations within major cell types, including monocytes, CD4+ and CD8+ T cells, NK cells, cDCs, pDCs, B cells and especially plasma cells. Expansion of unique subpopulations enriched in ISGs and/or in monogenic Lupus-associated genes classified patients with the highest DA. Profiling of ~82,000 single PBMCs from adult SLE patients confirmed the expansion of similar subpopulations in patients with the highest DA. This study lays the groundwork for resolving the origin of the SLE transcriptional signatures and the disease heterogeneity towards precision medicine applications. Patient demographics, clinical and laboratory data and treatment are summarized and available. The genomic data for participant aHD2 will not be included in the dataset The study description is reprinted from Nehar-Belaid et. al. Nature Immunology, 2020, with permission from Nature Immunology Group

  Study phs002048

• An RCOR1 loss-associated gene expression signature identifies a prognostically significant DLBCL subgroup

  Effective treatment of diffuse large B cell lymphoma (DLBCL) is plagued by heterogeneous responses to standard therapy, and molecular mechanisms underlying unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148 genomes with 91 matching transcriptomes in an R-CHOP-treated DLBCL cohort to uncover molecular subgroups linked to treatment failure. Systematic integration of high-resolution genotyping arrays and RNA-seq data revealed novel deletions in RCOR1 to be associated with unfavorable progression free survival (P = 0.001). Integration of expression data from the clinical samples with data from RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss-associated gene signature comprising of 233 genes. This signature identified a subgroup of patients with unfavorable overall survival (OS) (P = 0.023). The prognostic significance of the 233-gene signature for OS was reproduced in an independent cohort comprising of 195 R- CHOP treated patients (P = 0.039). Additionally, we discovered that within the IPI low risk group, the gene signature provides additional prognostic value that was independent of the cell-of-origin phenotype. Taken together, we present a novel and reproducible molecular subgroup of DLBCL, impacting risk-stratification of R- CHOP treated DLBCL patients and revealing a new avenue for therapeutic intervention strategies.

  Study EGAS00001001000