PanGraph: scalable bacterial pan-genome graph construction

Abstract

The genomic diversity of microbes is commonly parameterized as single nucleotide polymorphisms relative to a reference genome of a well-characterized, but arbitrary, isolate. However, any reference genome contains only a fraction of the microbial pangenome, the total set of genes observed in a given species. Reference-based approaches are thus blind to the dynamics of the accessory genome, as well as variation within gene order and copy number. With the wide-spread usage of long-read sequencing, the number of high-quality, complete genome assemblies has increased dramatically. Traditional computational approaches towards whole-genome analysis either scale poorly with the number of genomes, or treat genomes as dissociated "bags of genes", and thus are not suited for this new era. Here, we present PanGraph, a Julia-based library and command line interface for aligning whole genomes into a graph. Each genome is represented as an undirected path along vertices, which in turn, encapsulate homologous multiple sequence alignments. The resultant data structure succinctly summarizes population-level nucleotide and structural polymorphisms and can be exported into a several common formats for either downstream analysis or immediate visualization.