Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
- University of Toronto, Canada
- Nunavik Regional Board of Health and Social Services, Canada
- The Research Institute of McGill University Health Centre, Canada
- 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.
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Deep sequencing of a major TB outbreak in the Canadian ArcticNCBI SRA Bioproject, PRJNA549270.
Article and author information
Author details
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.
Reviewing Editor
- Miles P Davenport, University of New South Wales, Australia
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.
Version history
- 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)
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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Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
eLife 9:e53245.
https://doi.org/10.7554/eLife.53245
Further reading
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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