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Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission
Whole genome sequencing in conjunction with traditional epidemiology has been used to reconstruct transmission networks of Mycobacterium tuberculosis during outbreaks. Given its low mutation rate, genetic diversity within M. tuberculosis outbreaks can be extremely limited – making it difficult to de...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Microbiology Society
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249434/ https://www.ncbi.nlm.nih.gov/pubmed/30303479 http://dx.doi.org/10.1099/mgen.0.000217 |
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author | Martin, Michael A. Lee, Robyn S. Cowley, Lauren A. Gardy, Jennifer L. Hanage, William P. |
author_facet | Martin, Michael A. Lee, Robyn S. Cowley, Lauren A. Gardy, Jennifer L. Hanage, William P. |
author_sort | Martin, Michael A. |
collection | PubMed |
description | Whole genome sequencing in conjunction with traditional epidemiology has been used to reconstruct transmission networks of Mycobacterium tuberculosis during outbreaks. Given its low mutation rate, genetic diversity within M. tuberculosis outbreaks can be extremely limited – making it difficult to determine precisely who transmitted to whom. In addition to consensus SNPs (cSNPs), examining heterogeneous alleles (hSNPs) has been proposed to improve resolution. However, few studies have examined the potential biases in detecting these hSNPs. Here, we analysed genome sequence data from 25 specimens from British Columbia, Canada. Specimens were sequenced to a depth of 112–296×. We observed biases in read depth, base quality, strand distribution and read placement where possible hSNPs were initially identified, so we applied conservative filters to reduce false positives. Overall, there was phylogenetic concordance between the observed 2542 cSNP and 63 hSNP loci. Furthermore, we identified hSNPs shared exclusively by epidemiologically linked patients, supporting their use in transmission inferences. We conclude that hSNPs may add resolution to transmission networks, particularly where the overall genetic diversity is low. |
format | Online Article Text |
id | pubmed-6249434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Microbiology Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-62494342018-11-26 Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission Martin, Michael A. Lee, Robyn S. Cowley, Lauren A. Gardy, Jennifer L. Hanage, William P. Microb Genom Methods Paper Whole genome sequencing in conjunction with traditional epidemiology has been used to reconstruct transmission networks of Mycobacterium tuberculosis during outbreaks. Given its low mutation rate, genetic diversity within M. tuberculosis outbreaks can be extremely limited – making it difficult to determine precisely who transmitted to whom. In addition to consensus SNPs (cSNPs), examining heterogeneous alleles (hSNPs) has been proposed to improve resolution. However, few studies have examined the potential biases in detecting these hSNPs. Here, we analysed genome sequence data from 25 specimens from British Columbia, Canada. Specimens were sequenced to a depth of 112–296×. We observed biases in read depth, base quality, strand distribution and read placement where possible hSNPs were initially identified, so we applied conservative filters to reduce false positives. Overall, there was phylogenetic concordance between the observed 2542 cSNP and 63 hSNP loci. Furthermore, we identified hSNPs shared exclusively by epidemiologically linked patients, supporting their use in transmission inferences. We conclude that hSNPs may add resolution to transmission networks, particularly where the overall genetic diversity is low. Microbiology Society 2018-10-11 /pmc/articles/PMC6249434/ /pubmed/30303479 http://dx.doi.org/10.1099/mgen.0.000217 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Methods Paper Martin, Michael A. Lee, Robyn S. Cowley, Lauren A. Gardy, Jennifer L. Hanage, William P. Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission |
title | Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission |
title_full | Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission |
title_fullStr | Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission |
title_full_unstemmed | Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission |
title_short | Within-host Mycobacterium tuberculosis diversity and its utility for inferences of transmission |
title_sort | within-host mycobacterium tuberculosis diversity and its utility for inferences of transmission |
topic | Methods Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249434/ https://www.ncbi.nlm.nih.gov/pubmed/30303479 http://dx.doi.org/10.1099/mgen.0.000217 |
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