TY - JOUR A1 - Kuronen, Juri A1 - Horsfield, Samuel T. A1 - Pöntinen, Anna K. A1 - Mallawaarachchi, Sudaraka A1 - Arredondo-Alonso, Sergio A1 - Thorpe, Harry A1 - Gladstone, Rebecca A. A1 - Willems, Rob J.L. A1 - Bentley, Stephen D. A1 - Croucher, Nicholas J. A1 - Pensar, Johan A1 - Lees, John A. A1 - Tonkin-Hill, Gerry A1 - Corander, Jukka T1 - Pangenome-spanning epistasis and coselection analysis via de Bruijn graphs Y1 - 2024/07/01 JF - Genome Research JO - Genome Research SP - 1081 EP - 1088 DO - 10.1101/gr.278485.123 VL - 34 IS - 7 UR - http://genome.cshlp.org/content/34/7/1081.abstract N2 - Studies of bacterial adaptation and evolution are hampered by the difficulty of measuring traits such as virulence, drug resistance, and transmissibility in large populations. In contrast, it is now feasible to obtain high-quality complete assemblies of many bacterial genomes thanks to scalable high-accuracy long-read sequencing technologies. To exploit this opportunity, we introduce a phenotype- and alignment-free method for discovering coselected and epistatically interacting genomic variation from genome assemblies covering both core and accessory parts of genomes. Our approach uses a compact colored de Bruijn graph to approximate the intragenome distances between pairs of loci for a collection of bacterial genomes to account for the impacts of linkage disequilibrium (LD). We demonstrate the versatility of our approach to efficiently identify associations between loci linked with drug resistance and adaptation to the hospital niche in the major human bacterial pathogens Streptococcus pneumoniae and Enterococcus faecalis. ER -