A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

TLDR

Strain‑specific genomic diversity in the Mycobacterium tuberculosis complex influences pathogenesis, virulence, transmissibility, host response, and drug‑resistance emergence, and several classification systems have been proposed. The authors aim to evaluate single‑nucleotide polymorphisms as robust markers for phylogenetic analysis of MTBC strains. They analyze SNPs as stable genetic variation markers across a global collection of 1,601 genomes. The study identified ~92 k SNPs, of which ~7 k are strain‑specific, and proposed 62 markers that together form a barcode covering all main lineages and more sublineages than existing methods, enabling classification of clinical isolates for evaluating therapeutics and vaccines.

Abstract

Abstract Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type.