PA mutational signature in HCC
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ABSTRACT:
PROVIDER: PRJEB39863 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Duocarmycin mutational signature in HepG2 cells
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Project description:Mutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG>TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer contextual patterns improves modeling of UV mutations, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.
2019-09-11 | GSE127966 | GEO
Project description:Colibactin, a potent genotoxin of Escherichia coli, causes DNA double strand breaks (DSBs). We investigated if colibactin creates a particular DNA damage signature in infected human cells. Genomic contexts of colibactin-induced DSBs were enriched for a distinct AT-rich hexameric sequence motif. A survey of somatic mutations at the colibactin target sites of several thousand cancer genomes revealed significant enrichment of the motif in colorectal cancers. Moreover, the exact break point location corresponded with mutational hot spots in these cancers corresponding to a distinct trinucleotide signature. This work provides evidence for a role of colibactin in the etiology of human cancer.
2020-04-22 | GSE145594 | GEO
Project description:Colibactin DNA damage signature indicates mutational impact in colorectal cancer
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Project description:Transcript abundance was measured in whole-body virgin male Drosophila serrata from 41 inbred lines that had diverged through 27 generations of mutation accumulation that were sexually selected Sexual selection is predicted to have widespread effects on the genetic variation generated by new mutations as a consequence of the genic capture of condition by male sexual traits. We manipulated the opportunity for sexual selection on males during 27 generations of mutation accumulation in inbred lines of Drosophila serrata, and used a microarray platform to investigate the effect of sexual selection on the expression of 2685 genes, representing a broad coverage of biological function. Sexual selection had little effect on mean gene expression levels, with only 4 genes diverging significantly at a false discovery rate of 5% . In contrast, sexual selection impacted on both the magnitude and nature of mutational variance accumulating in these genes. The magnitude of mutational variance increased under sexual selection by an average of 29%. Mutational variance was less commonly generated by extreme phenotypes less commonly under sexual selection. Furthermore, analysis of random sets of five genes revealed that the mutational variance that accumulated under sexual selection was less pleiotropic in nature than that found in the absence of sexual selection. The generation of greater mutational variance without a general concomitant change in mean expression under sexual selection suggested that gene expression traits were be under apparent rather than direct sexual selection. We discuss two main explanations for the broad-based increase in mutational variance under sexual selection that both require extensive pleiotropy between traits affecting male mating success, standard metric traits represented here by gene expression traits, and general fitness. We measured gene expression of male Drosophila serrata from 41 mutation accumulation lines (whole-body) that were sexually selected. Data from two replicates for each line are presented.
2014-03-01 | E-GEOD-54777 | biostudies-arrayexpress
Project description:Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light
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Project description:<p>International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not been identified by conventional epidemiology yet potentially make a substantial contribution to cancer burden1. This pertains to clear cell renal cell carcinoma (ccRCC), for which obesity, hypertension, and tobacco smoking are risk factors but do not explain its geographical variation in incidence2. Some carcinogens generate somatic mutations and a complementary strategy for detecting past exposures is to sequence the genomes of cancers from populations with different incidence rates and infer underlying causes from differences in patterns of somatic mutations. Here, we sequenced 962 ccRCC from 11 countries of varying incidence. Somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures likely caused by extracts of Aristolochia plants were present in most cases and rare elsewhere. In Japan, a mutational signature of unknown cause was found in >70% cases and <2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher kidney cancer incidence rates (p-value <6 × 10−18). Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension suggesting non-mutagenic mechanisms of action underlying these risk factors. The results indicate the existence of multiple, geographically variable, mutagenic exposures potentially affecting 10s of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Geographic variation of mutagenic exposures in kidney cancer genomes – patient metadata files (<strong>Mutographs</strong>) associated with this study are available in the <strong>European Genome-Phenome Archive</strong>: https://ega-archive.org/datasets/EGAD00001012223.</p>
2024-03-26 | MTBLS9394 | MetaboLights
Project description:Transcript abundance was measured in whole-body virgin male Drosophila serrata from 41 inbred lines that had diverged through 27 generations of mutation accumulation. Pleiotropic mutations are the ultimate source of genetic variation in complex traits, including many human diseases. However, the nature and extent of mutational pleiotropy remain largely unknown. Here, we investigate the variation in 11,604 gene expression traits among 41 mutation accumulation lines of Drosophila serrata, which had diverged for 27 generations. We detected significant mutational variance in 4.6% of ESTs, but 70% of ESTs were invariant among lines, allowing us to reject a null hypothesis of phenome-wide universal pleiotropy. Mutational covariance among ESTs was detected at a frequency of only 1 in 193 random pairs of variable EST, bu t was detected among random combinations of five ESTs in 1 in 5 cases, revealing that mutational covariance among multiple ESTs was common. The observed frequency of significant multivariate covariance among random ESTs implied that a substantial number of ESTs (>70) must be pleiotropically affected by at least some mutations. We measured gene expression of male Drosophila serrata from 41 mutation accumulation lines (whole-body). Data from two replicates for each line are presented.
2013-09-01 | E-GEOD-49815 | biostudies-arrayexpress
Project description:The aim of this project is to test whether HPV oncogenes and /or interferon induce the APOBEC mutational signature in vitro, and to test the role of APOBEC3A in this process.
| EGAS00001002988 | EGA
Project description:P. aeruginosa mutational resistome
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