Maast: genotyping thousands of microbial strains efficiently

Abstract

Genotyping single nucleotide polymorphisms (SNPs) of intraspecific genomes is a prerequisite to performing population genetic analysis and microbial epidemiology. However, existing algorithms fail to scale for species with thousands of sequenced strains, nor do they account for the biased sampling of strains that has produced considerable redundancy in genome databases. Here we present Maast, a tool that reduces the computational burden of SNP genotyping by leveraging this genomic redundancy. Maast implements a novel algorithm to dynamically identify a minimum set of phylogenetically diverse conspecific genomes that contains the maximum number of SNPs above a user-specified allele frequency. Then it uses these genomes to construct a SNP panel for each species. A species SNP panel enables Maast to rapidly genotype thousands of strains using a hybrid of whole-genome alignment and k-mer exact matching. Maast works with both genome assemblies and unassembled sequencing reads. Compared to existing genotyping methods, Maast is more accurate and up to two orders of magnitude faster. We demonstrate Maasts utility on species with thousands of genomes by reconstructing the genetic structure of Helicobacter pylori across the globe and tracking SARS-CoV-2 diversification during the COVID-19 outbreak. Maast is a fast, reliable SNP genotyping tool that empowers population genetic meta-analysis of microbes at an unrivaled scale. Availabilitysource code of Maast is available at https://github.com/zjshi/Maast. Contactkpollard@gladstone.ucsf.edu