Simple combination of multiple somatic variant callers to increase accuracy

Authors

Alexander J Trevarton
Jeffrey T Chang
W Fraser Symmans

Publication Date

5-25-2023

Journal

Scientific Reports

Abstract

Publications comparing variant caller algorithms present discordant results with contradictory rankings. Caller performances are inconsistent and wide ranging, and dependent upon input data, application, parameter settings, and evaluation metric. With no single variant caller emerging as a superior standard, combinations or ensembles of variant callers have appeared in the literature. In this study, a whole genome somatic reference standard was used to derive principles to guide strategies for combining variant calls. Then, manually annotated variants called from the whole exome sequencing of a tumor were used to corroborate these general principles. Finally, we examined the ability of these principles to reduce noise in targeted sequencing.

Keywords

Humans, High-Throughput Nucleotide Sequencing, Algorithms, Neoplasms, Exome, Genome, Human, Polymorphism, Single Nucleotide, Software