Benchmarking of germline copy number variant callers from whole genome sequencing data for clinical applications.

ABSTRACT:

Motivation

Whole-genome sequencing (WGS) is increasingly preferred for clinical applications due to its comprehensive coverage, effectiveness in detecting copy number variants (CNVs), and declining costs. However, systematic evaluations of WGS CNV callers tailored to germline clinical testing-where high sensitivity and confirmation of reported CNVs are essential-remain necessary. Clinical reporting typically emphasizes CNVs affecting coding regions over precise breakpoint detection. This study benchmarks several short-read WGS CNV detection tools using reference cell lines to inform their clinical use.

Results

While tools vary in sensitivity (7%-83%) and precision (1%-76%), few meet the sensitivity needed for clinical testing. Callers generally perform better for deletions (

SUBMITTER: De La Vega FM 

PROVIDER: S-EPMC12005901 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature