7205 results for "({!join from=dataset_studies to=id v=$q1}) OR ("transcriptome" OR "RNA-seq" OR "rna sequencing" OR "rna-sequencing")"

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• Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma

  Background:Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples. Methods:Intra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed. Results:Sequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment were observed and led to a switch from a hot to a cold immune profile in three patients. Conclusions:This comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support

  Study EGAS00001005328

• BLUEPRINT RNA-seq of Epigenetic programming during monocyte to macrophage differentiation and trained innate immunity

  Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. Transcriptomes and epigenomes in four primary cell types: monocytes, in vitro differentiated naïve, tolerized and trained macrophages were characterized. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and pathways functionally implicated in trained immunity were identified. Strikingly, β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in DNase I hypersensitive sites at cell-type specific epigenetic loci unveiled differentiation and treatment specific repertoires. Altogether, this study provides a resource to understand the epigenetic changes that underlie innate immunity in humans.

  Study EGAS00001000953

• Spatial atlas of human atherosclerosis highlights role of the microvasculature in disease

  Atherosclerosis is a pervasive contributor to ischemic heart disease and stroke. Despite the advance of lipid lowering-therapies and antihypertensive agents, the residual risk of an atherosclerotic event remains high and developing therapeutic strategies has proven challenging. This is due to the complexity of atherosclerosis with a spatial interplay of multiple cell types within the vascular wall. Here we generate an integrative high-resolution map of human atherosclerotic plaques combining single-cell RNA-seq from multiple studies and spatial transcriptomics data from 12 human specimens, with different stages of atherosclerosis. We show cell-type and atherosclerosis-specific expression changes and spatially constrained alterations in cell-cell communication. We highlight the possible recruitment of lymphocytes via ACKR1 endothelial cells of the vasa vasorum, the migration of vascular smooth muscle cells towards the lumen by transforming into fibromyocytes, and cell-cell communication in the plaque region, indicating an intricate cellular interplay within the adventitia and the subendothelial space in human atherosclerosis.

  Study EGAS50000000660

• Spatial Transcriptomics Uncovers Tumor Microenvironment-Based Subtypes in Invasive Lobular Carcinoma

  Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer (BC); however, little is known about its tumor microenvironment (TME). Here, we investigated the spatial architecture of 43 hormone-receptor-positive, HER2-negative (HR+/HER2-) primary ILC samples, using spatial transcriptomics and detailed morphological annotation. By integrating morphology, spatial, and single-cell data, we mapped TME-related cell types, exploring their proximity to tumor cells and their enrichment in specific compartments. Clustering of spatial transcriptomics spots revealed significant inter- and intra-tumor heterogeneity, identifying pathways and cell types linked with disease outcomes. Morphological and gene expression data were finally integrated with a multimodal approach, leading to the identification of 4 new ILC subtypes based on TME heterogeneity. By using derived, specific gene expression signatures, these subtypes were identified and validated in external bulk RNA-seq/microarray datasets (SCAN-B and METABRIC), where differences in prognosis emerged.

  Study EGAS50000001001

• Integrative understanding of human immune system by functional genomics and development of intervention strategies for the prevention of autoimmune diseases

  To elucidate the regulation of gene expression in immune cell subsets and its contribution to autoimmune diseases, Whole blood and various immune cell subsets from 119 Systemic Lupus Erythematosus (SLE), 65 Dermatomyositis & Polymyositis, 67 Systemic Sclerosis, 19 Mixed Connective Tissue Disease, 18 Sjogren's syndrome, 24 Rheumatoid Arthritis, 23 Behcet's disease, 18 Adult Onset Still���s Disease, 25 ANCA-associated Vasculitis, 16 Takayasu���s Arteritis and 141 healthy controls (C) were collected (Naive_CD4, Mem_CD4, Fr._I_nTreg, Fr._II_eTreg, Fr._III_T, Th1, Th2, Th17, Tfh, NK, Naive_CD8, Mem_CD8, EM_CD8, CM_CD8, TEMRA_CD8, Naive_B, USM_B, SM_B, DN_B, Plasmablast, CL_Mono (or CD16n_Mono), CD16p_Mono, Int_Mono, NC_Mono, mDC, pDC, LDG, Neu). Whole genome sequencing was performed with whole blood samples. RNA-seq was performed with each immune cell subset samples. After filtering and normalization of the gene expression data, eQTL analysis was performed in each immune cell type. 15 immune cell subsets ATAC-seq was also performed in 8 SLE and HCs, each.

  Study JGAS000220

• RNA_seq_of_Toxoplasma_gondii_response_in_human_macrophages

  Toxoplasmosis is a zoonotic disease caused by a ubiquitous protozoan parasite called Toxoplasma gondii, which caninfect all mammal and bird species throughout the world. seroprevalence varies widely between countries. Studieshave estimated that between 7-34% of people in the UK have been infected with T. gondii. The vast majority of thesepeople will not have noticed any symptoms, however about 10% of people develop a mild to moderate self limitingflu-like illness. Following the acute active stage of the infection the parasite persists in the body in the form of cysts,particularly in heart and skeletal muscle and nervous system tissues, for many years, and usually for life. Inimmunocompetent persons these cysts do not pose a health risk. We will use RNA-seq to quantify the transcriptionalresponse of macrophages to T gondii infection.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 EGAS00001001708

• Single_Cell_RNAseq_at_various_stages_of_HiPSCs_differentiating_toward_definitive_endoderm_and_endoderm_derived_lineages

  When comparing the differentiation capacities of pluripotent stem cell lines that have different genetic backgrounds, batch to batch experimental variablility poses a significant challenge, especially when trying to identify smaller effects. One way to address this issue is to differentiate several different lines in the same culture dish, thereby elimating experimental variation. In addition, it allows researchers to analyze many more lines with less experiments. Parallel single cell RNA-Seq exploits that individual cells are tagged and hence each cell can be reliably assigned to the donor of origin based on the genetic variants it contains. In addition, analyzing the genetic signature of single cells within a differentiating population can reveal differentation stages that are not easily detected in bulk RNAseq data. 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 EGAS00001002278

• Molecular and clinical diversity in primary central nervous system lymphoma: a LOC network multi-omic PCNSL study

  Primary central nervous system lymphoma (PCNSL) is a distinct extranodal lymphoma presenting with limited stage disease but variable response rates to treatment despite homogenous pathological presentation. The likely underlying molecular heterogeneity and its clinical impact is poorly understood. The present dataset contents paired-ended whole-exome sequencing information (n=115; HyperExome Kapa hyperprep), paired-ended RNA-seq information (n=123; KAPA mRNA HyperPrep Kits), and paired-ended bisulfite sequencing (n=64; TruSeq Methyl Capture EPIC) from fresh-frozen tumor tissue immunocompetent, treatment naïve PCNSL patients. Additionally, the dataset includes single-ended RNA-seq (n=93; QuantSeq 3’ mRNA-Seq Library Prep Kit) from formalin-fixed, paraffin-embedded tissue of immunocompetent, treatment naïve PCNSL patients. All samples were sequenced in an Illumina NovaSeq 6000 instrument.

  Dataset EGAD00001008706

• TK-EPN862 - Patient-dervied xenograft model of Posterior Fossa A Ependymoma - RNAseq

  Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, patients who survive treatment for the most common subtype of pediatric EPN (posterior fossa A (PFA)), often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of PFA EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenge in propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models

  Study EGAS00001006844

• Acetalax and bisacodyl triple-negative breast cancer RNA-Seq

  Analysis of gene expression in triple negative breast cancer xenografts exhibiting good or bad response upon acetalax and bisacodyl treament.

  Study EGAS50000000618