Short-read aligner performance in germline variant identification

Abstract

Motivation: Read alignment is an essential first step in the characterization of DNA sequence variation. The accuracy of variant-calling results depends not only on the quality of read alignment and variant-calling software but also on the interaction between these complex software tools. Results: In this review, we evaluate short-read aligner performance with the goal of optimizing germline variant-calling accuracy. We examine the performance of three general-purpose short-read aligners - BWA-MEM, Bowtie 2, and Arioc - in conjunction with three germline variant callers: DeepVariant, FreeBayes, and GATK HaplotypeCaller. We discuss the behavior of the read aligners with regard to the data elements on which the variant callers rely, and illustrate how the runtime configurations of these software tools combine to affect variant-calling performance.