Evaluating Bioinformatics Processing of Somatic Variant Detection in cfDNA Using Targeted Sequencing with UMIs.

ABSTRACT: Circulating tumor DNA (ctDNA) is a promising cancer biomarker, but accurately detecting tumor mutations in cell-free DNA (cfDNA) is challenging due to their low frequency and sequencing errors. Our study benchmarked Mutect2, VarScan2, shearwater, and DREAMS-vc using deep targeted sequencing of cfDNA with Unique Molecular Identifiers (UMIs) from 111 colorectal cancer patients. Performance was assessed at both the mutation level (distinguish tumor variants from errors) and the sample level (detect if an individual has cancer). Additionally, we investigated the effects of various UMI grouping and consensus strategies. The shearwater-AND variant calling method demonstrated the highest precision in detecting tumor-derived mutations from plasma, and reached the highest ROC-AUC of 0.984 for sampl

SUBMITTER: Lin Y 

PROVIDER: S-EPMC11546253 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature