Whole-genome sequencing of 32 Coriell human cell lines
Short-read whole-genome sequencing (srWGS) 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 srWGS CNV callers tailored to germline clinical testing—where high sensitivity and confirmation of reported CNVs are essential—remain necessary. This study benchmarks several short-read WGS CNV detection tools using a set of 32 reference cell lines with known CNVs to inform their clinical use. Cell lines were sequenced on the Illumina NovaSeq 6000 with 2×150 bp paired-end libraries using the Illumina PCR-free library protocol at Tempus Lab, Inc. (Chicago, IL, USA)  Reads were mapped and aligned with DRAGEN v4.2 using the multi-genome B38 human genome reference. The provided BAMs can be used to reproduce the benchmarking results in the associated paper and to benchmark new CNV callers using the same data. See the associated paper for reference calls and VCF call sets on this data from a number of CNV calling algorithms tested in the study.