Genome graphs reveal the importance of structural variation in Mycobacterium tuberculosis evolution and drug resistance

Abstract

Structural variants (SVs) are increasingly recognized as key drivers of bacterial evolution, yet their role has not been explored thoroughly. This is due to limitations in traditional short-read sequencing and linear reference-based analyses, which can miss complex structural changes. Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), remains a major global health concern. In this study, we harness long-read sequencing technologies and genome graph tools to construct a Mtb pangenome reference graph (PRG) from 859 high-quality, diverse, long-read assemblies. To enable accurate genotyping of SVs leveraging the PRG, we developed miniwalk, a tool that outperforms a traditio..