Ontology highlight
ABSTRACT:
PROVIDER: PRJEB45759 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This dataset contained raw sequencing fastq data of the article "A body map of somatic mutagenesis in morphologically normal human tissues". We sampled morphologically normal tissue biopsies from 5 donors. We performed low-depth WGS on 1,764 samples, high-depth WGS on 48 samples and WES on 1,772 samples.
| EGAD00001007859 | EGA
Project description:Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each) of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In esophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometers were frequently seen, whereas in tissues like colon, rectum, and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue micro-structures. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.
| EGAS00001005458 | EGA
Project description:With aging, normal human tissues experience expansion of somatic clones that carry cancer mutations. However, whether such clonal expansion exists in the non-neoplastic intestine remains unknown. Here, from whole exome sequencing of 76 clonal human colon organoids, we identify a unique pattern of somatic mutagenesis in the inflamed epithelium of ulcerative colitis patients. The affected epithelium accumulates somatic mutations in multiple IL-17 signaling-related genes, including NFKBIZ, ZC3H12A, and PIGR, which are rarely identified in colon cancer. Targeted sequencing validates pervasive spread of IL-17 signaling-related mutations. Unbiased CRISPR-based knockout screening in colon organoids illuminates mutation-mediated resistance to IL-17A-induced proapoptotic response. Some of these genetic mutations are known to exacerbate experimental colitis in mice, and somatic mutagenesis in human colon epithelium may be causally linked to the inflammatory process. Our findings highlight a unique genetic landscape adapting to a hostile microenvironment and its potential contribution to the pathogenesis of ulcerative colitis.
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Project description:RNA-Seq of human individual tissues and mixture of 16 tissues (Illumina Body Map)
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Project description:The Applied Biosystems Tissue Gene Expression Database, known as the Human Body Map, is a collection of gene expression profiles from 31 normal tissues and a Universal Human Reference RNA (Stratagene). The Human BodyMap was created using the Applied Biosystems Expression Array System. There were three replicates per tissue for a total of 96 microarrays. Keywords: Human tissue whole genome survey
2007-06-04 | GSE7905 | GEO
Project description:We report the application of single molecule-based sequencing technology in combination with CXXC affinity purifcation (CAP-seq), MBD affinity purification (MAP-seq) and chromatin immunoprecipitation (ChIP-seq) to generate reciprocal methylation and chromatin modifcation maps in human and mouse. We find that contrary to sequence based prediction methods that humans and mice possess highly equivalent compliments of CpG islands (CGIs). The majority of these CGIs are positive for the active histone modification; H3K4me3 in embryonic stem cells (ES cells) the magnitude of which is correlated with the local density of non-methylated CpG. Approximately half of the human and mouse CGIs are distal to annotated gene promoters, yet more than 40% identify unanticipated transcription start sites as defined by RNA polymerase occupancy and published RNA mapping data. These orphans CGIs preferentially acquire DNA methylation in somatic cells, and this corresponds with a loss of H3K4me3 and RNA polymerase II at these sites. Conversely abnormal CGI methylation found in colorectal tumours showed a distinct distribution relative to that found in normal somatic tissues displaying preferential association with loci marked by H3K27me3 in human ES cells. This study provides a comprehensive functional assessment of CGIs in normal and diseased tissues. Examination of CGI methylation status in human and mouse primary tissues.
2010-10-04 | E-GEOD-21442 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of normal and tumoral tissues of the breast. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450 thousand CpGs in fresh frozen tissue samples (40 primary breast tumours and 17 normal breast tissues). Samples included morphologically normal samples of each tissue and tumor samples.
2015-02-04 | GSE52865 | GEO
Project description:Somatic L1 retrotransposition events have been shown to occur in epithelial cancers1-8. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases, but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds and many were present in multiple tumor sections implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth. We assessed the impact of somatic L1 insertions on the expression of the corresponding protein-coding genes by comparing protein abundance in the polyp with the highest number of somatic L1 insertions with that of its paired normal colon using mass spectrometry analysis. Of the 10 validated somatic insertions that were in protein coding regions in the polyp, two proteins – KIAA1217 and WARS2 – were downregulated in the adenoma >90% and >70%, respectively.
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Project description:The roles of topoisomerases in somatic mutagenesis in cancer are poorly understood and their DNA-binding landscape remains largely unmapped. Here we generated genome-wide DNA-binding maps of TOP2B, CTCF, and RAD21 in human hepatocellular carcinoma samples.
2024-02-01 | E-MTAB-13301 | biostudies-arrayexpress