Fast and accurate alignment of long bisulfite-seq reads

Summary: Longer sequencing reads, with at least 200 bases per template are now common. While traditional aligners have adopted new strategies to improve the mapping of longer reads, aligners specific to bisulfite-sequencing were optimized when much shorter reads were the norm. We sought to perform the first comparison using longer reads to determine which aligners were most accurate and efficient and to evaluate a novel software tool, bwa-meth, built on a traditional mapper that supports insertions, deletions and clipped alignments. We gauge accuracy by comparing the number of on and off-target reads from a targeted sequencing project and by simulations. Availability and Implementation: The benchmarking scripts and the bwa-meth software are available at https://github/com/brentp/bwa-meth/ under the MIT License.