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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 t...

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Autores principales: Lee, Robyn S, Proulx, Jean-François, McIntosh, Fiona, Behr, Marcel A, Hanage, William P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012596/
https://www.ncbi.nlm.nih.gov/pubmed/32014110
http://dx.doi.org/10.7554/eLife.53245
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author Lee, Robyn S
Proulx, Jean-François
McIntosh, Fiona
Behr, Marcel A
Hanage, William P
author_facet Lee, Robyn S
Proulx, Jean-François
McIntosh, Fiona
Behr, Marcel A
Hanage, William P
author_sort Lee, Robyn S
collection PubMed
description 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 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.
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spelling pubmed-70125962020-02-12 Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing Lee, Robyn S Proulx, Jean-François McIntosh, Fiona Behr, Marcel A Hanage, William P eLife Epidemiology and Global Health 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 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. eLife Sciences Publications, Ltd 2020-02-04 /pmc/articles/PMC7012596/ /pubmed/32014110 http://dx.doi.org/10.7554/eLife.53245 Text en © 2020, Lee et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Epidemiology and Global Health
Lee, Robyn S
Proulx, Jean-François
McIntosh, Fiona
Behr, Marcel A
Hanage, William P
Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
title Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
title_full Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
title_fullStr Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
title_full_unstemmed Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
title_short Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing
title_sort previously undetected super-spreading of mycobacterium tuberculosis revealed by deep sequencing
topic Epidemiology and Global Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012596/
https://www.ncbi.nlm.nih.gov/pubmed/32014110
http://dx.doi.org/10.7554/eLife.53245
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