Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1010353 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25780085.fastq.gz | Fastqsanger.gz | |||
| SRR25780086.fastq.gz | Fastqsanger.gz | |||
| SRR25780087.fastq.gz | Fastqsanger.gz | |||
| SRR25780088.fastq.gz | Fastqsanger.gz | |||
| SRR25780089.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:APOBEC3s-related somatic mutations are the predominant burden in biliary tract cancers (BTCs). Here, we reveal the effects and mechanisms of APOBEC3A/3B functional polymorphisms on cholangiocarcinoma and gallbladder cancer (GBC). rs2267401-G at the APOBEC3B promoter decreases cholangiocarcinoma risk but increased GBC risk. rs2267401-G confers a decreased APOBEC3B promoter activity in cholangiocarcinoma cells but an increased activity in GBC cells. rs12157810-C at the APOBEC3A promoter decreases the risk of BTCs. rs12157810-C up-regulated the promoter activity in both cells. APOBEC3A overexpression attenuates cancer evolution via causing apoptosis, in contrast to APOBEC3B. Inflammatory factors promote cancer evolution via interacting with transcriptional repressors regulating the APOBEC3A/3B promoters. ATAC-seq was used to identify the difference between transcriptional networks of cholangiocarcinoma and GBC.
2022-01-07 | GSE166372 | GEO
Project description:<a href="https://www.nature.com/articles/s41467-017-00493-9" target="_blank">Chen T-W, Lee C-C, Liu H, Wu C-S, Pickering CR, Huang P-J, et al., Nature Communications 8, Article number: 465 (2017) doi:10.1038/s41467-017-00493-9</a></p><p>Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n=188; p=0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B-/-:89A3B+/-:27A3B+/+), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.</p><br/><p>Mass Spectrometry Data Sets, Provided Below</p><p>The APOBEC-associated mutational signature enriched in the OSCC-Taiwan cohort was investigated to determine if this mutational signature might correlate with tumor-related alterations in APOBEC expression.</p><p>RNA-Seq results from normal / tumor paired tissue samples were analyzed and data may be obtain from NCBI (<a href="https://www.ncbi.nlm.nih.gov/bioproject/PRJNA327548" target="_blank">BioProject:PRJNA327548</a> and <a href="https://trace.ncbi.nlm.nih.gov/Traces/sra/sra.cgi?study=SRP078156" target="_blank">SRA Study:SRP078156</a>). </p><p>Corresponding enrichment of A3A-specific peptides in tumor proteomes was assessed by iTRAQ (isobaric Tags for Relative and Absolute Quantification) mass spectrometry protein quantification methods in 38 normal / tumor paired tissue samples. Peptides were digested, labeled by iTRAQ, and fractionated by on-line 2D-HPLC to 44 fractions. Each dataset (labeled as OSCC-Pxx, example OSCC-P01) contains 44 raw mass spectrometry data files (LTQ-Orbitrap ELITE). The iTRAQ 114 reagent was used to label the digestion products of 30-pairs of OSCC tissues, and iTRAQ 115 and 116 reagents were used to label peptides of non-tumor tissue and tumor tissue, respectively. The APOBEC3A (A3A) coding region is part of a APOBEC3 gene cluster at 22q13.</p><ul><li>Dataset imported into MassIVE from <a href="https://cptac-data-portal.georgetown.edu/cptac/s/S034">https://cptac-data-portal.georgetown.edu/cptac/s/S034</a> on 08/28/19</li></ul>
2019-08-28 | MSV000084250 | MassIVE
Project description:The utility of RADseq in an experimental setting is also demonstrated, based on our chasacterisation of an APOBEC mutation signature in an APOBEC3A transfected mouse cell line. 0D5 cells, derived from SSM3 cells, were co-transfected with a mixture containing pcDNA3.1 vectors expressing either APOBEC3A or APOBEC3B (kindly donated by Vincent Caval), pcDNA3.1 construct expressing deaminase null APOBEC3A linked to a uracil deglycosylase construct and a plasmid encoding mutant GFP and WT mCherry that is a reporter for APOBEC mutagenesis. Cells were grown, and gDNA extracted, prior to preparation of RADseq libraries using a PstI- MspI double-digest. Libraries underwent a Pippin Prep to select fragments in the size range of 220-520 bp (genomic sequence plus 148 bp of adapters). Single-end sequencing (1x101bp) was performed on an Illumina NovaSeq6000 utilizing v1.5 chemistry. Reads were aligned to mm10 using bwa mem and variants called using the GATK4 pipeline.
2023-06-30 | GSE234146 | GEO
Project description:The APOBEC3 cytosine deaminases are implicated as the cause of a prevalent somatic mutation pattern found in cancer genomes. The APOBEC3 enzymes act as viral restriction factors by mutating viral genomes. Mutation of the cellular genome is presumed to be an off-target activity of the enzymes, although the regulatory measures for APOBEC3 expression and activity remain undefined. It is therefore difficult to predict the circumstances that enable APOBEC3 interaction with cellular DNA that leads to mutagenesis. The APOBEC3A (A3A) enzyme is the most potent deaminase of the family. Using proteomics, we evaluated protein interactors of A3A to identify potential regulators. We found that A3A interacts with the Chaperonin Containing TCP-1 (CCT) complex, a cellular machine that assists in protein folding and function. Importantly, depletion of CCT resulted in increased A3A-induced cytotoxicity. Evaluation of cancer genomes demonstrated an enrichment of A3A mutational signatures in cancers with silencing mutations in CCT subunit genes. Together, these data suggest that the CCT complex interacts with A3A, and that disruption of CCT function results in increased A3A mutational activity.
2021-07-02 | PXD024191 | Pride
Project description:The APOBEC3 (A3) family of cytidine deaminases induce somatic mutations that are highly prevalent in cancers, but the functional consequences are largely unknown. To determine functional consequences we exposed MCF7 tumorigenic breast epithelial cells to APOBEC3A, APOBEC3B or APOBEC3H Haplotype I. Comparative analysis between cells pre and post -APOBEC3 exposure revealed fewer deamination-dependent γH2AX foci post-APOBEC3 exposure, despite maintaining A3 protein expression. In a mouse xenograft model, high expressing, but not low expressing APOBEC3A-exposed cells caused increased tumor progression. In contrast, high expressing, but not low expressing APOBEC3B-exposed cells decreased tumor size. APOBEC3H Haplotype I-exposed cells stochastically increased tumor progression independent of expression levels. Consistent with tumor data, RNA-seq showed upregulation of tumor enhancing pathways only in cells that enhanced tumor progressiongrowth. The results indicate that in a breast cancer xenograft model, APOBEC3A and APOBEC3H Haplotype I are more likely to contribute to enhanced tumor progression than APOBEC3B.
2026-01-08 | GSE262252 | GEO
Project description:We aimed to decipher APOBEC3A driven mutational differences in human PDX_PDAC tissues. 40 human PDX_PDAC tissues were grouped based on their APOBEC3A expression levels into APOBEC3A High and Low groups. Illumina whole exome sequencing (WES) was performed and downstream variant analysis was applied.
2021-09-06 | E-MTAB-10115 | biostudies-arrayexpress
Project description:The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here, APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in human cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts overexpressed genes and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B mediates R-loop homeostasis and contributes to R-loop mutagenesis in cancer.
2023-06-10 | GSE148581 | GEO
Project description:Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Cytokine treatments can diminish HBV cccDNA via APOBEC3-mediated deamination. Here we show that overexpression of APOBEC3A alone, however, was not sufficient to reduce cccDNA in HBV-infected cells. This required addition of interferon indicating that cccDNA degradation requires an additional, interferon-stimulated gene (ISG). Transcriptome analyses identified ISG20 as the only type I and II interferon-induced, nucleus-resident protein with annotated nuclease activity. ISG20 expression was detected in human livers in acute, self-limiting but not in chronic hepatitis B. ISG20 depletion abolished the interferon-induced loss of cccDNA, and co-expression of ISG20 and APOBEC3A was sufficient to diminish cccDNA. In conclusion, non-cytolytic HBV cccDNA decline requires induction of a deaminase and nuclease. Our findings highlight that ISGs cooperate for their antiviral function and this cooperativity may be explored for therapeutic targeting.
2021-04-22 | PXD019285 | Pride
Project description:Buffering of deleterious mutations by molecular chaperones and degradation of aberrant proteins by quality control systems are both major factors that can impact the mutational landscape available to a client protein. The impacts of the proteostasis network on protein evolution are not limited to just endogenous clients, but can also shape the mutational landscapes accessible to rapidly evolving viral proteins. Here, we test the hypothesis that the composition of the host cell’s endoplasmic reticulum (ER) proteostasis network shapes the evolution of RNA viruses by focusing on human immunodeficiency virus-1 envelope (Env), a membrane glycoprotein that folds and matures in the host cell’s secretory pathway. We apply chemical genetic methods to activate the IRE1-XBP1s and/or the ATF6 transcriptional arms of the unfolded protein response in a stress-independent manner. We then quantitatively assess the impact of the resulting altered host cell ER proteostasis environments on the relative enrichment of all Env single amino acid substitutions using deep mutational scanning. We find that upregulation of host ER proteostasis factors globally reduces the mutational tolerance of HIV-1 Env, particularly upon induction of the IRE1-XBP1s transcriptional arm of the UPR. The effects of ATF6 activation are less global, but still significant at particular Env sites. The impact of the XBP1s-induced ER proteostasis environment is disparate for diverse structural elements of Env. Conserved, functionally important regions generally exhibit the largest decreases in mutational tolerance upon XBP1s activation. In contrast, specific regions of Env, including regions targeted by broadly neutralizing antibodies, display greatly enhanced mutational tolerance when XBP1s is activated. Altogether, these data reveal a new set of host factors that specifically shape the mutational space accessible to HIV Env and, more generally, provide compelling evidence that UPR-regulated proteostasis mechanisms play critical roles in membrane protein evolution.
2022-01-30 | GSE171356 | GEO