cfSNV: a software tool for the sensitive detection of somatic mutations from cell-free DNA

Cell-free DNA (cfDNA) in blood, viewed as a surrogate for tumor biopsy, has many clinical applications, including diagnosing cancer, guiding cancer treatment and monitoring treatment response. All these applications depend on an indispensable, yet underdeveloped task: detecting somatic mutations from cfDNA. The task is challenging because of the low tumor fraction in cfDNA. Recently, we developed the computational method cfSNV, the first method that comprehensively considers the properties of cfDNA for the sensitive detection of mutations from cfDNA. cfSNV vastly outperformed the conventional methods that were developed primarily for calling mutations from solid tumor tissues. cfSNV can accurately detect mutations in cfDNA even with medium-coverage (e.g., ≥200×) sequencing, which makes whole-exome sequencing (WES) of cfDNA a viable option for various clinical utilities. Here, we present a user-friendly cfSNV package that exhibits fast computation and convenient user options. We also built a Docker image of it, which is designed to enable researchers and clinicians with a limited computational background to easily carry out analyses on both high-performance computing platforms and local computers. Mutation calling from a standard preprocessed WES dataset (~250× and ~70 million base pair target size) can be carried out in 3 h on a server with eight virtual CPUs and 32 GB of random access memory.