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<p>Tuberculosis (TB) is typically attributed to a single infecting strain of the <i>Mycobacterium tuberculosis</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月19日

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  • Jacob E. Munro,
  • Anna K. Coussens,
  • Melanie Bahlo

摘要

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.