TBtypeR: Sensitive detection and sublineage classification of Mycobacterium tuberculosis complex mixed-strain infections

Munro, JE; Coussens, AK; Bahlo, M

Author(s): Munro, JE; Coussens, AK; Bahlo, M;
Details: Publication Year 2025-02-19,Volume 8,Issue #1,Page 260
Journal Title: Communications Biology
Abstract: Tuberculosis (TB) is typically attributed to a single infecting strain of the Mycobacterium tuberculosis Complex (MTBC), however mixed-strain infections are more common than reported due to the limitations of conventional diagnostics. While whole genome sequencing (WGS) methods have improved the detection of mixed-strain infections, existing tools struggle to reliably identify mixed-strain infections with frequencies below 10%. TBtypeR, a new tool, addresses this challenge by comparing WGS data to a phylogenetic SNP panel of over 10,000 sites and 164 MTBC phylotypes and using a model based on the binomial distribution to classify sublineage mixtures at frequencies as low as 1%. Extensive benchmarking shows TBtypeR outperforms current methods. Application to a published dataset of 5000 WGS samples identified 305 mixed-strain infections, six-fold higher than previously reported. The TBtypeR R package and a Nextflow pipeline are available at github.com/bahlolab/TBtypeR, providing a powerful tool for studying TB epidemiology and mixed-strain infections.
Publisher: Springer Nature
Keywords: *Mycobacterium tuberculosis/genetics/classification/isolation & purification; *Tuberculosis/microbiology/diagnosis; Humans; Phylogeny; Whole Genome Sequencing; Polymorphism, Single Nucleotide; Genome, Bacterial; *Coinfection/microbiology
Research Division(s): Genetics and Gene Regulation; Infection and Global Health
PubMed ID: 39972208
Publisher's Version: https://doi.org/10.1038/s42003-025-07705-9
Open Access at Publisher's Site: https://doi.org/10.1038/s42003-025-07705-9
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-09-23 08:17:30

Last Modified: 2025-09-23 08:17:47