Author response: Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing [peer_review]

Robyn S Lee, Jean-François Proulx, Fiona McIntosh, Marcel A Behr, William P Hanage
2020 unpublished
Tuberculosis disproportionately affects the Canadian Inuit. To address this, it is imperative we understand transmission dynamics in this population. We investigate whether 'deep' sequencing can provide additional resolution compared to standard sequencing, using a wellcharacterized outbreak from the Arctic (2011-2012, 50 cases). Samples were sequenced to~500-1000x and reads were aligned to a novel local reference genome generated with PacBio SMRT sequencing. Consensus and heterogeneous
more » ... terogeneous variants were identified and compared across genomes. In contrast with previous genomic analyses using~50x depth, deep sequencing allowed us to identify a novel super-spreader who likely transmitted to up to 17 other cases during the outbreak (35% of the remaining cases that year). It is increasingly evident that within-host diversity should be incorporated into transmission analyses; deep sequencing may facilitate more accurate detection of super-spreaders and transmission clusters. This has implications not only for TB, but all genomic studies of transmission -regardless of pathogen. Lee et al. eLife 2020;9:e53245. DOI: 1 of 15 RESEARCH ARTICLE Lee et al. eLife 2020;9:e53245.
doi:10.7554/elife.53245.sa2 fatcat:squyrmberbhg5i7ppklbvte4jy