Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing

  1. Robyn S Lee  Is a corresponding author
  2. Jean-François Proulx
  3. Fiona McIntosh
  4. Marcel A Behr
  5. William P Hanage
  1. University of Toronto, Canada
  2. Nunavik Regional Board of Health and Social Services, Canada
  3. The Research Institute of McGill University Health Centre, Canada
  4. Harvard TH Chan School of Public Health, United States

Abstract

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.

Data availability

Sequencing data and the assembly for MT-0080 are available on the NCBI's Sequence Read Archive under BioProject PRJNA549270.

The following data sets were generated

Article and author information

Author details

  1. Robyn S Lee

    Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
    For correspondence
    robyn.s.c.lee@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7120-9053
  2. Jean-François Proulx

    Nunavik Regional Board of Health and Social Services, Kuujjuaq, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Fiona McIntosh

    The Research Institute of McGill University Health Centre, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Marcel A Behr

    The Research Institute of McGill University Health Centre, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. William P Hanage

    Center for Communicable Disease Dynamics, Harvard TH Chan School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

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.

Ethics

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.

Reviewing Editor

  1. Miles P Davenport, University of New South Wales, Australia

Publication history

  1. Received: November 1, 2019
  2. Accepted: January 19, 2020
  3. Accepted Manuscript published: February 4, 2020 (version 1)
  4. Version of Record published: February 11, 2020 (version 2)

Copyright

© 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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  1. Robyn S Lee
  2. Jean-François Proulx
  3. Fiona McIntosh
  4. Marcel A Behr
  5. William P Hanage
(2020)
Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
eLife 9:e53245.
https://doi.org/10.7554/eLife.53245

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