A Universal Duplex Sequencing Approach for Accurate Detection of Somatic Mutations.

ABSTRACT: Ultra-accurate detection of rare somatic mutations is critical for understanding mutational processes in human disease, aging, and environmental exposures, yet current methods are limited by error rates, restricted genome coverage, and high DNA input. We present UDSeq, a duplex sequencing protocol combining random fragmentation, efficient UMI ligation, and quantitative input control to achieve near-complete genome/exome representation from as little as 100 pg DNA. Benchmarking in human sperm estimates a UDSeq error rate of ~2.5×10^-9 per base pair. UDSeq captures mutational signatures from heterogeneous populations without clonal expansion, reproduces exposure-specific patterns in cell lines and rodent models, and enables cross-species profiling. Compared with prior duplex method

SUBMITTER: Nandi SP 

PROVIDER: S-EPMC12458366 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature