Search Results - EGA European Genome-Phenome Archive

RNA sequencing in primary inflammatory (TPP) macrophages treated with a MEK1/2 inhibitor

By investigating an intergenic haplotype on chr21q22, independently linked to inflammatory bowel disease (IBD), ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis, we discover that the causal gene, ETS2, is a master regulator of inflammatory responses in human macrophages and delineate how the risk haplotype increases ETS2 expression. Using a database of cellular signatures, we identified drugs that could modulate this pathway. To validate the anti-inflammatory activity of one class of small molecules in vitro, we treated TPP macrophages with vehicle control or a selective, non-ATP competitive MEK inhibitor (PD-0325901) at 2 doses (100nM and 500nM) and performed RNA sequencing.

Study EGAS00001007552

Comprehensive Deep Sequencing Atlas in HCC tumors

Establishment of a comprehensive deep sequencing atlas focused on Hepatocellular Carcinoma (HCC) tumors, employing Whole Genome Sequencing (WGS), RNA Sequencing (RNAseq), and Whole Exome Sequencing (WES). The atlas aims to unravel the intricate genetic landscape of HCC, providing a detailed characterization of genomic alterations, transcriptomic profiles, and key mutations associated with this liver cancer. The integration of WGS, RNAseq, and WES data offers a holistic perspective, facilitating a deeper understanding of the molecular mechanisms driving HCC pathogenesis. The resulting atlas serves as a valuable resource for researchers, clinicians, and the broader scientific community, contributing to advancements in HCC diagnostics, prognostics, and therapeutic interventions.

Study EGAS00001007694

Isala Citizen Science Project: Cross-sectional branch

The Isala Citizen Science Project, is named after the first female doctor in Belgium, Isala Van Diest (1842-1916). In a co-creative way, volunteers provided samples and data, proposed research objectives and survey questions, and helped to disseminate and interpret the objectives and results through different media platforms, jointly breaking taboos on women’s and vaginal health. In Flow 1, we collected a single sample from a cross-section of the population, characterized the microbiome, and associated it with data collected in questionnaires. Here, we provide extensive sample meta-data for over 3000 women who completed questionnaires on their lifestyle, diet, health, contraceptive use and environment.

Study EGAS00001006934

RNA sequencing of a glioblastoma PDX cohort

Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of glioma PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in glioblastoma. In summary, we reported a newly established and molecularly characterized panel of glioma PDX models with high relevance for translational preclinical research.

Study EGAS00001007119

Targeted sequencing of follicular lymphoma tumour samples from the UK's Haematological Malignancy Research Network

Follicular lymphoma displays morphological and clinical heterogeneity, underpinned by shared molecular pathogenesis. Mutations in epigenetic regulators alongside t(14;18) have been identified as disease initiating events. Additional mutational diversity suggests disease heterogeneity. Whether this resolves into mechanistically distinct subsets remains an open question. Targeted sequencing was applied to an unselected population-based FL cohort (n=548) diagnosed in a catchment population of ~4 million (14 centers), with full clinical follow-up (n=538) that included 96 DLBCL transformations. We investigated whether molecular subclusters of FL can be identified, and whether mutational data provide predictive information relating to transformation.

Study EGAS00001005238

Neutrophils infected with Leishmania donovani

In the context of studying visceral leishmaniasis, neutrophils infected with Leishmania donovani have been compared to uninfected neutrophils. Compared time points are 0, 6 and 24 hours post infection. Neutrophils of three human donors have been used. Overall 6 samples for infected neutrophils at time point 6 hours and 6 samples for infected neutrophils at time point 24 hours exist, including three biological samples and two technical samples. Uninfected neutrophils represent 3 samples at time point 0 hours, 3 samples at time point 6 hours and 3 samples at time point 24 hours. Transcriptome of Leishmania donovani culture has been assessed in two replicates.

Study EGAS00001004912

High titers and low fucosylation of early phase anti-SARS-CoV-2 IgG promote hyper-inflammation by alveolar macrophages

We show that early phase anti-Spike IgG in serum of critically ill COVID-19 patients induces hyper-inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for severe COVID-19. First, inflammation is driven by high titers of anti-Spike IgG, a hallmark of severe disease. Second, we found that anti-Spike IgG from severely ill patients is intrinsically more pro-inflammatory because of different glycosylation of the Fc tail, particularly by low fucosylation. This dataset is linked with the following ArrayExpress Experiment: E-MTAB-10431 - 2020_COVID19_FCGR_MIL10_IgGfucosylation

Study EGAS00001005206

Mongolia Western HCC

Mongolia has the world’s highest incidence of hepatocellular carcinoma (HCC), with ~100 cases/105 inhabitants. We molecularly characterize the Mongolian (n=192) compared to Western HCCs (n=187) by RNA-seq and WES. Mongolian patients were predominantly younger, female, with HBV-HDV non-cirrhotic livers. Mongolian HCCs had higher rates of protein-coding mutations (121 vs 70 mut /tumor in West), and mutations in known (i.e. APOB) and putative HCC drivers (TSC2). A novel mutational signature (SBS Mongolia) was identified in 25% of cases associated with the carcinogenic DMS genotoxic signature. Two unique molecular classes enriched in HBV-HDV infection, female gender and inflamed tumors are described.

Study EGAS00001005364

SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]

CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through sporadically emerging escape mutations in MHC- I restricted viral epitopes.

Study EGAS00001005060

Detection of Cancer Mutations by Urine Liquid Biopsy in Bladder Cancer Patients

The management of bladder cancer faces multiple challenges concerning the diagnostics and fol-low-up approaches. The standard diagnostic test is invasive cystoscopy. Urine cytology and re-cently proposed urine-based biomarkers still could not replace cystoscopy, thus prompting calls for improvements. Here, we explore urine liquid biopsy to detect cancer mutations for therapeutic and prognostic assessment and subsequently evaluate the utility of urine as a suitable specimen in diagnosing bladder cancer. Our findings show that the analysis of pre-and post-operative urine enables the characterization of specific tumor mutations, which can be used to diagnose and evaluate a patient’s prognosis and therapy response.

Study EGAS00001005758

Deciphering somatic mosaic structural variation in human blood lineages using single-cell multiomics

Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood. Using haplotype-resolved single-cell multi-omics, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).

Study EGAS00001006567

Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in ICI-related pneumonitis

ICI-pneumonitis is a frequent serious adverse event of cancer immunotherapy hinging on a cell-mediated immune response, though the exact pathophysiology is currently unknown. Using single-cell transcriptomics, an enrichment of pathogenic (TBX21, RORC, IFNG, IL17A, CSF2 expressing) T-helper 17.1 cells and pro-inflammatory (TNF, IL1B, IL6, IL23A expressing) monocytes was identified in ICI-pneumonitis bronchoalveolar lavage fluid, putatively engaging in a feedforward inflammatory loop. This finding yields several novel therapeutic targets for the treatment of ICI-pneumonitis. Most notably repurposing anti-IL-23 merits further research as a potential efficacious and safe treatment for ICI-pneumonitis.

Study EGAS00001006762

Methylation-based classification of human mesenchymal chondrosarcoma

We applied methylome and copy number profiling to a set of 45 well characterized MCS cases to evaluate their potential diagnostic value. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. Methylome profiling represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. It can furthermore aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.

Study EGAS00001007042

Pre-existing immunity drives the response to neoadjuvant chemotherapy in esophageal adenocarcinoma

Esophageal adenocarcinoma (EAC) is a highly aggressive tumor. Patients with locally advanced disease undergo neoadjuvant chemotherapy (nCT) before surgery, however fewer than 30% of treated patients achieve a pathological complete response associated with increased 5-year overall survival. We set out to elucidate the mechanisms the response to nCT by multi-dimensional profiling of pre-treatment tumor biopsies and blood samples from EAC patients. In particular we performed whole exome sequencing (WES) and RNAseq on n=26 baseline EAC tumor; two additional EAC samples underwent only WES. WES on matched peripheral blood mononuclear cells (PBMCs) were used as germline control.

Study EGAS00001007245

PRADO trial - Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab plus nivolumab in stage III melanoma

The PRADO trial tested a personalized response-directed treatment approach based on the pathologic response after neoadjuvant ipilimumab plus nivolumab in stage III melanoma patients. In patients achieving a major pathologic response, in their index lymph node (the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with partial response underwent TLND only, whereas patients with pathologic non-response underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Biomarker analyses based on baseline RNA sequencing data were performed in order to find features that are associated with major pathologic response.

Study EGAS00001007601

Assessment of epigenetic variation in human iPS cells-Medip

n order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs and from studies in the mouse, it appears that an epigenetic memory of the starting cell type is carried over to hiPSCs. However a comprehensive comparative study of the characteristics of these hiPSCs has been missing from the literature. Importantly studies which aimed to address these aspects of hiPSCs have used cells from different patients. In order to avoid this important confounding variable and to keep the genetic background constant, tissue samples were procured from the patients and reprogrammed to iPS cells. The methylation status of these iPS cells will be compared. Protocol: Primary cell cultures were generated and reprogrammed to iPS cells. DNA was extracted and immunoprecipitated using anti-methyl cytosine and anti-hydroxymethyl cytosine antibodies. 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 EGAD00001000827

13384 results for ""pdc"+"heritage+language"+census+study"

in 31.68 milliseconds.

RNA sequencing in primary inflammatory (TPP) macrophages treated with a MEK1/2 inhibitor

Comprehensive Deep Sequencing Atlas in HCC tumors

Isala Citizen Science Project: Cross-sectional branch

RNA sequencing of a glioblastoma PDX cohort

Targeted sequencing of follicular lymphoma tumour samples from the UK's Haematological Malignancy Research Network

Neutrophils infected with Leishmania donovani

High titers and low fucosylation of early phase anti-SARS-CoV-2 IgG promote hyper-inflammation by alveolar macrophages

Mongolia Western HCC

SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]

Detection of Cancer Mutations by Urine Liquid Biopsy in Bladder Cancer Patients

Deciphering somatic mosaic structural variation in human blood lineages using single-cell multiomics

Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in ICI-related pneumonitis

Methylation-based classification of human mesenchymal chondrosarcoma

Pre-existing immunity drives the response to neoadjuvant chemotherapy in esophageal adenocarcinoma

PRADO trial - Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab plus nivolumab in stage III melanoma

Assessment of epigenetic variation in human iPS cells-Medip

Genome and transcriptome sequence data from a metastatic high-grade adenocarcinoma of the fallopian tubes patient

Genome and transcriptome sequence data from a metastatic carcinoma to paraspinal mass with primary unknown patient

Genome and transcriptome sequence data from a metastatic leiomyosarcoma patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a squamous cell lung carcinoma patient

Genome and transcriptome sequence data from a metastatic gastric cancer patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a leiomyosarcoma patient

Genome and transcriptome sequence data from a meningioma patient

Genome and transcriptome sequence data from a abdominal sarcoma patient

Genome and transcriptome sequence data from a metastatic rectal cancer patient

Genome and transcriptome sequence data from a metastatic melanoma patient

Genome and transcriptome sequence data from a metastatic leiomyosarcoma patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a metastatic pancreatic cancer patient

Genome and transcriptome sequence data from a metastatic pancreatic cancer patient

Genome and transcriptome sequence data from a metastatic colon cancer patient

Genome and transcriptome sequence data from a metastatic serous ovarian cancer patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a T-cell prolymphocytic leukemia patient

Genome and transcriptome sequence data from a diffuse large B-cell lymphoma patient

Genome and transcriptome sequence data from a metastatic adrenocortical carcinoma patient

Genome and transcriptome sequence data from a metastatic neuroendocrine tumor, lung primary patient

Genome and transcriptome sequence data from a metastatic choroidal melanoma patient

Genome and transcriptome sequence data from a metastatic pancreatic cancer patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a metastatic ovarian cancer patient

Genome and transcriptome sequence data from a metastatic melanoma patient

Genome and transcriptome sequence data from a metastatic pancreatic adenocarcinoma patient

Genome and transcriptome sequence data from a metastatic sarcomatoid carcinoma of the lung patient