Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32569800.fastq.gz | Fastqsanger.gz | |||
| SRR32569800_1.fastq.gz | Fastqsanger.gz | |||
| SRR32569800_2.fastq.gz | Fastqsanger.gz | |||
| SRR32569801.fastq.gz | Fastqsanger.gz | |||
| SRR32569801_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:APOBEC cytidine deaminase enzymes play a crucial role in antiviral innate immunity as they introduce mutations in viral genomes, restrict viral replication, and promote host defense against infections. Special three-stranded nucleic acid structures, called R-loops, have been considered as efficient targets for APOBEC-mediated mutagenesis because they present an ideal substrate, a persistent single-stranded DNA, for the enzyme. However, the relationship between R-loops and APOBEC enzyme activity has not been verified and remains to be elucidated. Here, we reveal a mechanistic link between R-loop formation, APOBEC enzyme binding, and APOBEC mutagenesis at viral R-loop targets during virus infection. In a cellular model involving human T lymphoblastoid leukemia cells infected with Herpes simplex virus 1 (HSV-1), we show that APOBEC3A and APOBEC3G binding sites and mutagenesis signatures occur mainly in viral R-loop structures. C-to-T mutagenesis primarily targets R-loops, which are specifically concentrated in HSV-1 genes that are essential for virus assembly and function. Among these genes, we identified mutation hotspots resulting in amino acid changes, likely leading to inactivation of HSV-1 protein functions. Collectively, our findings show that viral R-loops serve as potent targets for APOBEC-induced mutagenesis, representing an effective strategy to inactivate essential viral proteins and compromise viral activity.
2026-03-11 | GSE277995 | GEO
Project description:APOBEC cytidine deaminase enzymes play a crucial role in antiviral innate immunity as they introduce mutations in viral genomes, restrict viral replication, and promote host defense against infections. Special three-stranded nucleic acid structures, called R-loops, have been considered as efficient targets for APOBEC-mediated mutagenesis because they present an ideal substrate, a persistent single-stranded DNA, for the enzyme. However, the relationship between R-loops and APOBEC enzyme activity has not been verified and remains to be elucidated. Here, we reveal a mechanistic link between R-loop formation, APOBEC enzyme binding, and APOBEC mutagenesis at viral R-loop targets during virus infection. In a cellular model involving human T lymphoblastoid leukemia cells infected with Herpes simplex virus 1 (HSV-1), we show that APOBEC3A and APOBEC3G binding sites and mutagenesis signatures occur mainly in viral R-loop structures. C-to-T mutagenesis primarily targets R-loops, which are specifically concentrated in HSV-1 genes that are essential for virus assembly and function. Among these genes, we identified mutation hotspots resulting in amino acid changes, likely leading to inactivation of HSV-1 protein functions. Collectively, our findings show that viral R-loops serve as potent targets for APOBEC-induced mutagenesis, representing an effective strategy to inactivate essential viral proteins and compromise viral activity.
2026-03-11 | GSE284474 | GEO
Project description:APOBEC cytidine deaminase enzymes play a crucial role in antiviral innate immunity as they introduce mutations in viral genomes, restrict viral replication, and promote host defense against infections. Special three-stranded nucleic acid structures, called R-loops, have been considered as efficient targets for APOBEC-mediated mutagenesis because they present an ideal substrate, a persistent single-stranded DNA, for the enzyme. However, the relationship between R-loops and APOBEC enzyme activity has not been verified and remains to be elucidated. Here, we reveal a mechanistic link between R-loop formation, APOBEC enzyme binding, and APOBEC mutagenesis at viral R-loop targets during virus infection. In a cellular model involving human T lymphoblastoid leukemia cells infected with Herpes simplex virus 1 (HSV-1), we show that APOBEC3A and APOBEC3G binding sites and mutagenesis signatures occur mainly in viral R-loop structures. C-to-T mutagenesis primarily targets R-loops, which are specifically concentrated in HSV-1 genes that are essential for virus assembly and function. Among these genes, we identified mutation hotspots resulting in amino acid changes, likely leading to inactivation of HSV-1 protein functions. Collectively, our findings show that viral R-loops serve as potent targets for APOBEC-induced mutagenesis, representing an effective strategy to inactivate essential viral proteins and compromise viral activity.
2026-03-11 | GSE277996 | GEO
Project description:Intratumoral genetic heterogeneity and mutational burden have been suggested to be the fuel and the source of resistance for many molecularly targeted therapies throughout a multitude of cancers. Emerging evidence indicates that tumor cells could hijack the powerful mutagenesis machinery mediated by the DNA deaminase APOBEC family proteins to intensify mutagenesis, promote intratumoral heterogeneity, and foster therapy resistance through a cell-autonomous mechanism. However, this mechanism has yet to be characterized. Utilizing prostate cancer (PCa) as a relevant model, we have identified the Synaptotagmin Binding Cytoplasmic RNA Interacting Protein (SYNCRIP) as a molecular brake for APOBEC-driven mutagenesis, intratumoral heterogeneity, and resistance to Androgen Receptor (AR) targeted therapies. Through a multi-disciplinary approach integrating bulk and single cell RNA-Seq (scRNA-Seq), whole-genome exome-sequencing (WES), and CRISPR library screening, we identified eight mutated resistance driver genes and revealed unparalleled details of how these heterogeneously aberrant subclones fuel the evolution of AR therapy resistance. For the first time, these findings exposed a cell-autonomous mechanism activating APOBEC-driven mutagenesis, consequently fueling mutational burden, genetic heterogeneity, and therapy resistance, and suggested that APOBEC proteins could be the potential therapeutic targets for preventing or overcoming resistance in PCa.
2023-07-20 | GSE202321 | GEO
Project description:<p><b>Reprinted from Roberts et al. "An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers", Nature Genetics, 45:970-976, 2013, with permission of Nature Publishing Group:</b></p> <p>Recent studies indicate that a subclass of APOBEC cytidine deaminases, which convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction, may induce mutation clusters in human tumors. We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates with APOBEC mRNA levels. Mutation clusters in whole-genome and exome data sets conformed to the stringent criteria indicative of an APOBEC mutation pattern. Applying these criteria to 954,247 mutations in 2,680 exomes from 14 cancer types, mostly from The Cancer Genome Atlas (TCGA), showed a significant presence of the APOBEC mutation pattern in bladder, cervical, breast, head and neck, and lung cancers, reaching 68% of all mutations in some samples. Within breast cancer, the HER2-enriched subtype was clearly enriched for tumors with the APOBEC mutation pattern, suggesting that this type of mutagenesis is functionally linked with cancer development. The APOBEC mutation pattern also extended to cancer-associated genes, implying that ubiquitous APOBEC-mediated mutagenesis is carcinogenic.</p>
| phs000677 | dbGaP
Project description:Intratumor mutational heterogeneity has been documented in primary non-small cell lung cancer. Here, we elucidate mechanisms of tumor evolution and heterogeneity in metastatic thoracic tumors (lung adenocarcinoma and thymic carcinoma) using whole-exome and transcriptome sequencing, SNP array for copy number alterations (CNA) and mass spectrometry-based quantitative proteomics of metastases obtained by rapid autopsy. APOBEC-mutagenesis, promoted by increased expression of APOBEC3 region transcripts and associated with a high-risk germline APOBEC3 variant, strongly correlated with mutational tumor heterogeneity. TP53 mutation status was associated with APOBEC hypermutator status. Interferon pathways were enriched in tumors with high APOBEC mutagenesis and IFN- induced expression of APOBEC3B in lung adenocarcinoma cells in culture suggesting a role for the immune microenvironment in the generation of mutational heterogeneity. CNA occurring late in tumor evolution correlated with downstream transcriptomic and proteomic heterogeneity, although global proteomic heterogeneity was significantly greater than transcriptomic and CNA heterogeneity. These results illustrate key mechanisms underlying multi-dimensional heterogeneity in metastatic thoracic tumors.
2019-05-07 | PXD012845 | Pride
Project description:<p>Integrated proteo-genomics studies to characterize tumor heterogeneity of metastatic lung adenocarcinoma and thymic carcinoma are lacking. We carried out whole exome sequencing, RNA sequencing, copy number estimation and mass spectrometry-based proteomics of 40 tumors from five rapid/warm autopsy patients. We found highly variable mutational heterogeneity that was largely driven by APOBEC-mutagenesis with the expression of APOBEC3B (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=APOBEC3B">Gene ID: 9582</a>) and APOBEC3A_B (<a href="https://www.ncbi.nlm.nih.gov/gene/100913187">Gene ID: 100913187</a>) due to underlying APOBEC3 region germline variants as the likely mediating mechanism. APOBEC3A_B expression was associated with increased immune tumor microenvironment and CD274 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=CD274">Gene ID: 29126</a>) expression while smoking was associated with increased APOBEC-mutagenesis in TP53 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=TP53">Gene ID: 7157</a>) mutant tumors with high APOBEC3B expression. Heterogeneity at the level of the transcriptome and proteome occurred in association with copy number heterogeneity, not APOBEC-induced mutational heterogeneity. Arm and focal copy number alterations (CNAs) occurred as an evolutionarily late event in a subset of patients, with corresponding changes in the transcriptome and proteome, implicating CNAs as a driving force of heterogeneity in the evolution of metastatic disease.</p>
| phs001432 | dbGaP
Project description:APOBEC Cytidine Deaminase Mutagenesis Pattern is Widespread in Human Cancers
| PRJNA226256 | ENA
Project description:APOBEC Cytidine Deaminase Mutagenesis Pattern is Widespread in Human Cancers
| PRJNA226257 | ENA