Phylogenetic assignment of Mycobacterium tuberculosis Beijing clinical isolates in Japan by maximum a posteriori estimation

Abstract

Intra-species phylogeny of Mycobacterium tuberculosis has been regarded as a clue to estimate its potential risk to develop drug-resistance and various epidemiological tendencies. Genotypic characterization of variable number of tandem repeats (VNTR), a standard tool to ascertain transmission routes, has been improving as a public health effort, but determining phylogenetic information from those efforts alone is difficult. We present a platform based on maximum a posteriori (MAP) estimation to estimate phylogenetic information for M. tuberculosis clinical isolates from individual profiles of VNTR types. This study used 1245 M. tuberculosis clinical isolates obtained throughout Japan for construction of an MAP estimation formula. Two MAP estimation formulae, classification of Beijing family and other lineages, and classification of five Beijing sublineages (ST11/26, STK, ST3, and ST25/19 belonging to the ancient Beijing subfamily and modern Beijing subfamily), were created based on 24 loci VNTR (24Beijing-VNTR) profiles and phylogenetic information of the isolates. Recursive estimation based on the formulae showed high concordance with their authentic phylogeny by multi-locus sequence typing (MLST) of the isolates. The formulae might further support phylogenetic estimation of the Beijing lineage M. tuberculosis from the VNTR genotype with various geographic backgrounds. These results suggest that MAP estimation can function as a reliable probabilistic process to append phylogenetic information to VNTR genotypes of M. tuberculosis independently, which might improve the usage of genotyping data for control, understanding, prevention, and treatment of TB.

Keywords: Genotype; Maximum a posteriori; Mycobacterium tuberculosis; Phylogeny; VNTR.