Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission

Michael A Martin, Robyn S Lee, Lauren Cowley, Jennifer L Gardy, William P Hanage

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Whole genome sequencing in conjunction with traditional epidemiology has been used to reconstruct transmission networks of Mycobacterium tuberculosis during outbreaks. Given its low mutation rate, genetic diversity within M. tuberculosis outbreaks can be extremely limited – making it difficult to determine precisely who transmitted to whom. In addition to consensus SNPs (cSNPs), examining heterogeneous alleles (hSNPs) has been proposed to improve resolution. However, few studies have examined the potential biases in detecting these hSNPs. Here, we analysed genome sequence data from 25 specimens from British Columbia, Canada. Specimens were sequenced to a depth of 112–296×. We observed biases in read depth, base quality, strand distribution and read placement where possible hSNPs were initially identified, so we applied conservative filters to reduce false positives. Overall, there was phylogenetic concordance between the observed 2542 cSNP and 63 hSNP loci. Furthermore, we identified hSNPs shared exclusively by epidemiologically linked patients, supporting their use in transmission inferences. We conclude that hSNPs may add resolution to transmission networks, particularly where the overall genetic diversity is low.
Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMicrobial Genomics
Volume4
Issue number10
Early online date11 Oct 2018
DOIs
Publication statusPublished - Oct 2018

Keywords

  • Mycobacterium tuberculosis
  • genomic epidemiology
  • transmission
  • whole genome sequencing
  • within-host diversity

ASJC Scopus subject areas

  • Medicine(all)

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