ArticleCell systems2021
RepairSig: Deconvolution of DNA damage and repair contributions to the mutational landscape of cancer.
Article in Cell systems, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed.
- Topographical archetypes of somatic mutagenesis in cancer.bioRxiv : the preprint server for biology · 2026Article
- Combined inference of known and novel mutational signatures with ReDeNovo.bioRxiv : the preprint server for biology · 2026Article
- Toward identification of common DNA repair process in mutational signatures.bioRxiv : the preprint server for biology · 2026Article
- Damage and Misrepair Signatures: Compact Representations of Pan-cancer Mutational Processes.bioRxiv : the preprint server for biology · 2025Article
- Recent Advances in Genomic Approaches for the Detection of Homologous Recombination Deficiency.Cancer research and treatment · 2024Review
- MUSE-XAE: MUtational Signature Extraction with eXplainable AutoEncoder enhances tumour types classification.Bioinformatics (Oxford, England) · 2024Article
- Accurate and sensitive mutational signature analysis with MuSiCal.Nature genetics · 2024Article
- Cancer driver mutations: predictions and reality.Trends in molecular medicine · 2023Review
- Identification of multiplicatively acting modulatory mutational signatures in cancer.BMC bioinformatics · 2022Article
- Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy.Clinical science (London, England : 1979) · 2022Article
- Mutational Signatures: From Methods to Mechanisms.Annual review of biomedical data science · 2021Article
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5 authors.
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Abstract
Cancer genomes accumulate a large number of somatic mutations resulting from a combination of stochastic errors in DNA processing, cancer-related aberrations of the DNA repair machinery, or carcinogenic exposures; each mutagenic process leaves a characteristic mutational signature. A key challenge is understanding the interactions between signatures, particularly as DNA repair deficiencies often modify the effects of other mutagens. Here, we introduce RepairSig, a computational method that explicitly models additive primary mutagenic processes; non-additive secondary processes, which interact with the primary processes; and a mutation opportunity, that is, the distribution of sites across the genome that are vulnerable to damage or preferentially repaired. We demonstrate that RepairSig accurately recapitulates experimentally identified signatures, identifies autonomous signatures of deficient DNA repair processes, and explains mismatch repair deficiency in breast cancer by de novo inference of both primary and secondary signatures from patient data. RepairSig is freely available for download at https://github.com/ncbi/RepairSig.
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