ArticleNucleic acids research2022
Duplex-Repair enables highly accurate sequencing, despite DNA damage.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Methyltransferase-assisted single duplex sequencing for detecting circulating tumor DNA.EMBO molecular medicine · 2026Article
- High-fidelity rare structural variant detection with HiFiRE3 reduced representation via restriction enzyme ends.bioRxiv : the preprint server for biology · 2026Article
- Benchmarking of duplex sequencing approaches to reveal somatic mutation landscapes.bioRxiv : the preprint server for biology · 2025Article
- Modulating cell-free DNA biology as the next frontier in liquid biopsies.Trends in cell biology · 2025Review
- Methyl-CODEC enables simultaneous methylation and duplex sequencing.Nucleic acids research · 2025Article
- TopoQual polishes circular consensus sequencing data and accurately predicts quality scores.BMC bioinformatics · 2025Article
- Impact of Higher Cell-Free DNA Yields on Liquid Biopsy Testing in Glioblastoma Patients.Clinical chemistry · 2025Article
- Sensitive circulating tumor DNA-based residual disease detection in epithelial ovarian cancer.Life science alliance · 2024Article
- MAESTRO-Pool Enables Highly Parallel and Specific Mutation-Enrichment Sequencing for Minimal Residual Disease Detection in Cohort Studies.Clinical chemistry · 2024Article
- A critical spotlight on the paradigms of FFPE-DNA sequencing.Nucleic acids research · 2023Review
- Single duplex DNA sequencing with CODEC detects mutations with high sensitivity.Nature genetics · 2023Article
- Article
- Proceedings of the fifth international Molecular Pathological Epidemiology (MPE) meeting.Cancer causes & control : CCC · 2022Article
- Direct adenylation from 5'-OH-terminated oligonucleotides by a fusion enzyme containing Pfu RNA ligase and T4 polynucleotide kinase.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accurate DNA sequencing is crucial in biomedicine. Underlying the most accurate methods is the assumption that a mutation is true if altered bases are present on both strands of the DNA duplex. We now show that this assumption can be wrong. We establish that current methods to prepare DNA for sequencing, via 'End Repair/dA-Tailing,' may substantially resynthesize strands, leading amplifiable lesions or alterations on one strand to become indiscernible from true mutations on both strands. Indeed, we discovered that 7-17% and 32-57% of interior 'duplex base pairs' from cell-free DNA and formalin-fixed tumor biopsies, respectively, could be resynthesized in vitro and potentially introduce false mutations. To address this, we present Duplex-Repair, and show that it limits interior duplex base pair resynthesis by 8- to 464-fold, rescues the impact of induced DNA damage, and affords up to 8.9-fold more accurate duplex sequencing. Our study uncovers a major Achilles' heel in sequencing and offers a solution to restore high accuracy.
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