Alignment-free unique molecular identifier clustering suppresses sequencing errors for accurate detection of low-frequency DNA variants.

ABSTRACT: Accurate detection of low-frequency DNA variants (below 1%) is essential in diverse biological and clinical contexts, yet remains fundamentally constrained by the high intrinsic error rates of next-generation sequencing technologies. Although unique molecular identifiers (UMIs) have significantly mitigated these errors by uniquely indexing original template molecules, their efficacy is compromised by UMI collisions and by artifacts introduced during polymerase chain reaction (PCR) amplification and sequencing, which collectively engender false-positive variant calls. Here, we present AFUMIC, an alignment-free UMI clustering framework that systematically addresses these limitations through collision-resilient UMI grouping and a consensus quality score (CQS)-guided strategy for high-fidelity

SUBMITTER: Yu F 

PROVIDER: S-EPMC12452285 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature