Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
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 well-characterized 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 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 all 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.
Sequencing data and the assembly for MT-0080 are available on the NCBI's Sequence Read Archive under BioProject PRJNA549270.
Deep sequencing of a major TB outbreak in the Canadian ArcticNCBI SRA Bioproject, PRJNA549270.
Article and author information
National Institutes of Health (R01AI128344)
- William P Hanage
Canadian Institutes of Health Research (Fellowship 152448)
- Robyn S Lee
Canadian Institutes of Health Research (Foundation Award 148362)
- Marcel A Behr
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Ethics approval was obtained from the Institutional Review Board (IRB) of the Harvard T.H. Chan School of Public Health (IRB18-0552) and the IRB of McGill University Faculty of Medicine (IRB A02-M08-18A). Clinical and epidemiological data were previously collected as part of the routine public health response and all data was analyzed in non-nominal fashion, using unique identifiers, therefore individual patient consent was not required. This study was done in collaboration with the Nunavik Regional Board of Health and Social Services.
- Miles P Davenport, University of New South Wales, Australia
- Received: November 1, 2019
- Accepted: January 19, 2020
- Accepted Manuscript published: February 4, 2020 (version 1)
- Version of Record published: February 11, 2020 (version 2)
© 2020, Lee et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Funding This work is supported by the National Research Foundation Singapore (NRF-NRFF2017-02), PRECISION Health Research, Singapore (PRECISE) and the Agency for Science, Technology and Research (A*STAR). WP Koh was supported by National Medical Research Council, Singapore (NMRC/CSA/0055/2013). CC Khor was supported by National Research Foundation Singapore (NRF-NRFI2018-01). Rajkumar Dorajoo received a grant from the Agency for Science, Technology and Research Career Development Award (A*STAR CDA - 202D8090), and from Ministry of Health Healthy Longevity Catalyst Award (HLCA20Jan-0022). The Singapore Chinese Health Study was supported by grants from the National Medical Research Council, Singapore (NMRC/CIRG/1456/2016) and the U.S. National Institutes of Health [NIH] (R01 CA144034 and UM1 CA182876).
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