Manipulating base quality scores enables variant calling from bisulfite sequencing alignments using conventional Bayesian approaches

Abstract

Calling germline SNP variants from bisulfite-converted sequencing data poses a challenge for conventional tools, which have no inherent capability to dissociate true polymorphisms from artificial mutations induced by the chemical treatment. Nevertheless, SNP data is desirable both for genotyping and for resolving the interaction between genetic and epigenetic effects when elucidating the DNA methylome. The confounding effect of bisulfite conversion can be resolved by observing differences in allele counts on a per-strand basis. Herein, we present a computational pre-processing approach for adapting such data, thus enabling downstream analysis in this way using conventional variant calling software such as GATK or Freebayes.