ArticleNature genetics2025
A redefined InDel taxonomy provides insights into mutational signatures.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Integrating germline and tumor sequencing to improve hereditary cancer diagnosis and care.European journal of human genetics : EJHG · 2026Review
- Identification and validation of a previously missed mutational signature in colorectal cancer.Nature communications · 2026Article
- Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination.Nucleic acids research · 2026Article
- Distinct repair processes produce APOBEC-induced deletions, tandem substitutions, and complex mutations in yeast and human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- High-depth whole genome sequencing of premalignant breast lesions reveals rearrangement hotspots and personalized management opportunities.Nature communications · 2026Article
- MuRaL-indel: a deep learning framework for building insertion and deletion mutation rate maps.Briefings in bioinformatics · 2026Article
- IMPACT OF FLUORESCENT DYES ON MUTATIONS IN NEXT GENERATION SEQUENCING LIRBARY PREPARATION.bioRxiv : the preprint server for biology · 2026Article
- Unravelling genome-wide mosaic microsatellite mutations at single-cell resolution.bioRxiv : the preprint server for biology · 2026Article
- Low microsatellite instability revisited: a review.Virchows Archiv : an international journal of pathology · 2026Review
- IMPACT OF FLUORESCENT DYES ON MUTATIONS IN NEXT GENERATION SEQUENCING LIBRARY GENERATION.Journal of biomolecular techniques : JBT · 2026Article
- Collateral mutagenesis funnels multiple sources of DNA damage into a ubiquitous mutational signature.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
20 authors.
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Abstract
Despite their deleterious effects, small insertions and deletions (InDels) have received far less attention than substitutions. Here we generated isogenic CRISPR-edited human cellular models of postreplicative repair dysfunction (PRRd), including individual and combined gene edits of DNA mismatch repair (MMR) and replicative polymerases (Pol ε and Pol δ). Unique, diverse InDel mutational footprints were revealed. However, the prevailing InDel classification framework was unable to discriminate these InDel signatures from background mutagenesis and from each other. To address this, we developed an alternative InDel classification system that considers flanking sequences and informative motifs (for example, longer homopolymers), enabling unambiguous InDel classification into 89 subtypes. Through focused characterization of seven tumor types from the 100,000 Genomes Project, we uncovered 37 InDel signatures; 27 were new. In addition to unveiling previously hidden biological insights, we also developed PRRDetect-a highly specific classifier of PRRd status in tumors, with potential implications for immunotherapies.
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