Comprehensive Analysis of <i>Mycobacterium Tuberculosis</i> Genomes Reveals Important Variations in Bacterial Virulence

Tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), is a significant health problem worldwide. In the present study, we performed a comprehensive analysis of the genetic variation of Mtb. We developed an analysis method to detect large insertions and deletions (INDELs), which have been understudied previously. We analyzed 1,960 clinical isolates and identified single nucleotide variations (SNVs) as well as small and large INDELs. We found that large INDELs were enriched in the PE/PPE gene family, a group of repetitive genes that is hypothesized to be an important virulence factor. An evolutionary analysis revealed that Mtb genomes were enriched by slightly deleterious mutations. A genome-wide association study showed 31 variants associated with disease outcomes and drug resistance. Of these variants, nine were large INDELs and six were in PE/PPE genes. This study provides a comprehensive catalog of genetic variations and highlights their potential impact for the future treatment and risk prediction of tuberculosis.