11768 results for "cancer rna-seq"

in 14.96 milliseconds.

• HCA_Adrenal_Foetal_WSSS_RNA_SB

  The Human Cell Atlas initiative is an ambitious global research effort which aims to describe every cell in the human body across all developmental stages to generate a reference map to accelerate progress in science and medicine particularly relating to human development and disease. The initiative is led by investigators based at the Wellcome Sanger Institute and the Broad Institute of MIT and Harvard and funding support from the Wellcome and NIH. This specific project will assess human development. We aim to interrogate the cellular composition and molecular regulators underpinning development and maturation through single cell RNA-sequencing/spatial transcriptomics and computational algorithms to predict cellular developmental trajectories and cell-cell interactions. We will subsequent validate these findings in situ using allied imaging technologies e.g. immunohistochemistry and RNAscope and in vitro culture of human intestinal organoids (HIOs). 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 EGAS00001004089

• Offspring Sex Impacts DNA Methylation and Gene Expression in Placentae from Women with Diabetes during Pregnancy

  Exposure to diabetes in utero is known to increase the offspring's likelihood of developing metabolic disease in adulthood, but the mechanisms involved are unknown. It has been proposed that early exposure to hyperglycemia and elevated insulin levels may lead to malprogramming of the fetus leading to the subsequent development of diabetes and obesity. Epigenetic modifications of the genome including DNA methylation, provide a plausible mechanism that allows for permanent propagation of gene activity states from one generation of cells to the next. The placenta, a fetal tissue easily accessible for study, is a complex organ that is essential in regulating fetal growth. The changes in placental nutrient transport associated with diabetes during pregnancy (DDP) have significant effects on the developing fetus, indicating that the placenta plays a critical role in fetal programming. The aim of our study was to investigate whether exposure to DDP alters genome-wide DNA methylation in the placenta obtained from term pregnancies resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression.

  Study phs001535

• Tissue and Fluid Analysis in Ocular Inflammatory Disease

  Granulomas are found in multiple infectious and non-infectious human diseases, yet the pathogenic drivers of granulomatous disease are still poorly understood. To enrich for pathologic inflammatory cells, we leveraged the intrinsic immunologic isolation of the eye by examining granulomatous uveitis, a form of ocular inflammation. We performed single-cell RNA-sequencing to obtain an unbiased gene expression survey of ocular immune cells in the anterior chamber of four live human donors with granulomatous uveitis. We paired this with antigen-receptor sequence analysis to identify clonally expanded lymphocytes. Each individual had robust clonal expansion arising from a single T or B cell lineage, suggesting distinct pathogenic processes in each patient. This variability in clonal expansion was mirrored by individualized combinations of TH1, TH1/TH17, and Tregs in ocular CD4 T cells. In contrast, ocular CD8 T cells were more transcriptionally similar across donors. Finally, clonally expanded, activated B cells displayed evidence of plasmablast differentiation and class-switching within the ocular microenvironment. Collectively, our study identified conserved and individualized features of granulomatous inflammation, illuminating parallel pathophysiologic mechanisms.

  Study phs002449

• The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR)

  The Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) Registry and Repository, supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), was established in 2000 to provide a resource for the scientific community to explore genetic and non-genetic factors affecting rheumatoid arthritis (RA) occurrence and outcomes in African Americans. The long term objective is a database and a repository of 1,100 RA and 550 matched healthy African-American subjects. This CLEAR Registry and Repository has two arms: a longitudinal arm for subjects with early RA (enrollment from 2000 to 2005) and a cross-sectional arm for subjects with any disease duration (enrollment from 2006 to 2012). CLEAR has two components: a database and a repository. The database contains extensive demographic, socioeconomic, clinical and radiographic (radiographs of hands and feet) information and bone mineral density data from DEXA scans. The repository contains genomic DNA, plasma and serum on most of the participants. Participants in CLEAR II had RNA isolated from peripheral blood cells.

  Study phs001360

• Transcriptomics sequencing analysis of pre-invasive lung adenocarcinoma in never-smokers

  The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing for samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could categorize tumors into molecular subtypes within pathology-defined lesion types. These subtypes were linked with the advanced radiology-defined lesion type and coordinated with immune cell infiltration throughout the progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns, and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.

  Study EGAS50000000439

• Whole exome sequencing of pre-invasive lung adenocarcinoma in non-smokers

  The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing for samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could categorize tumors into molecular subtypes within pathology-defined lesion types. These subtypes were linked with the advanced radiology-defined lesion type and coordinated with immune cell infiltration throughout the progression of LUAD. Characterization of these lesion types identified positively selected mutation patterns, and suggested that angiogenesis of the late-stage AIS type potentially contributes to tissue invasion of the MIA type. Our findings offer a novel resource that may help to improve early diagnosis and patient prognosis, and also suggest possible approaches for early disease interception.

  Study EGAS50000000438

• 10x Multiome from Human Fetal Heart

  We hope to uncover the genetic basis of congenital heart disease by examining how genetic variants, especially those in non-coding regions, influence heart development. To achieve this goal, our research team created a single-cell atlas of human fetal heart development. The study population consists of 41 structurally normal fetal hearts spanning 6 to 22 weeks post-conception. We profiled close to 750,000 using single-cell RNA sequencing and ATAC sequencing technologies via the 10x Genomics Multiome platform.The molecular technologies employed allowed for simultaneous analysis of gene expression and chromatin accessibility at the single-cell level. This approach identified numerous distinct cell types and states within the developing heart, offering detailed insights into gene activity and enhancer usage during critical stages of heart development.Principal findings include the characterization of diverse cell populations and the identification of specific gene expression patterns and regulatory elements active during heart formation. This high-resolution atlas provides valuable insights into how genetic variants may disrupt normal heart development, particularly those in non-coding regions that affect gene regulation.

  Study phs003778

• Response​ to Tagraxofusp in Blastic Plasmacytoid Dendritic Cell Neoplasm

  Tagraxofusp is a CD123-targeted therapy comprised of a recombinant human interleukin-3 (IL-3) fused to a truncated diphtheria toxin (DT) payload. It is the first approved treatment specifically for patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). In order to identify biomarkers of response, bone marrow samples from 12 BPDCN patients who were treated with tagraxofusp in the pivotal phase II trial (NCT02113982) were profiled longitudinally using gene panel and/or single-cell RNA sequencing. Durable responders had either wildtype or missense TET2 mutations while transient and non-responders had at least one truncating TET2 mutation. Those who had progression at any one point during the treatment course (transient responders) and non-responders had enrichment of the chemokines CCL3, CCL4, and CCL5. Residual tumor cells following tagraxofusp treatment were identified in all patients, whose resistance may be due to their lower levels of TXNRD1 possibly preventing the potentiation of tagraxofusp. Thus, response to tagraxofusp may be related to culmination of intrinsic TET2 mutations, levels of TXNRD1, and extrinsic effects of chemokines within bone marrow.

  Study phs003895

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000416

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000418