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

• DOI: 10.1099/mgen.0.000217
• Publication Date: 2018-10-10T16:13:25Z
• Authors: Michael A. Martin; Robyn S. Lee; Lauren A. Cowley; Jennifer L. Gardy; William P. Hanage
• Keywords: Concordance

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. outbreaks can be extremely limited – making it difficult determine precisely who transmitted whom. In addition consensus SNPs (cSNPs), examining heterogeneous alleles (hSNPs) proposed improve resolution. However, few studies have examined the potential biases detecting these hSNPs. Here, we analysed sequence data from 25 specimens British Columbia, Canada. Specimens were sequenced a depth 112–296×. We observed read depth, base quality, strand distribution and placement where possible hSNPs initially identified, so applied conservative filters reduce false positives. Overall, there was phylogenetic concordance between 2542 cSNP 63 hSNP loci. Furthermore, identified shared exclusively by epidemiologically linked patients, supporting their use inferences. conclude that may add resolution networks, particularly overall is low.