A fast and agnostic method for bacterial genome-wide association studies: Bridging the gap between k-mers and genetic events

by Magali Jaillard, Leandro Lima, Maud Tournoud, Pierre Mah é, Alex van Belkum, Vincent Lacroix, Laurent Jacob

Genome-wide association study (GWAS) methods applied to bacterial genomes have shown promising results for genetic marker discovery or detailed assessment of marker effect. Recently, alignment-free methods based on k-mer composition have proven their ability to explore the accessory genome. Howeve r, they lead to redundant descriptions and results which are sometimes hard to interpret. Here we introduce DBGWAS, an extended k-mer-based GWAS method producing interpretable genetic variants associated with distinct phenotypes. Relying on compacted De Bruijn graphs (cDBG), our method gathers cDBG nodes, identified by the association model, into subgraphs defined from their neighbourhood in the initial cDBG. DBGWAS is alignment-free and only requires a set of contigs and phenotypes. In particular, it does not require prior annotation or reference genomes. It produces subgraphs representing ph enotype-associated genetic variants such as local polymorphisms and mobile genetic elements (MGE). It offers a graphical framework which helps interpret GWAS results. Importantly it is also computationally efficient—experiments took one hour and a half on average. We validated our method using ant ibiotic resistance phenotypes for three bacterial species. DBGWAS recovered known resistance determinants such as mutations in core genes inMycobacterium tuberculosis, and genes acquired...

Source: PLoS Genetics - November 12, 2018 Category: Genetics & Stem Cells Authors: Magali Jaillard Source Type: research