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Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis

Detecting factors associated with transmission is important to understand disease epidemics, and to design effective public health measures. Clustering and terminal branch lengths (TBL) analyses are commonly applied to genomic data sets of Mycobacterium tuberculosis (MTB) to identify sub-populations...

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Autor principal: Menardo, Fabrizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239681/
https://www.ncbi.nlm.nih.gov/pubmed/35762734
http://dx.doi.org/10.7554/eLife.76780
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author Menardo, Fabrizio
author_facet Menardo, Fabrizio
author_sort Menardo, Fabrizio
collection PubMed
description Detecting factors associated with transmission is important to understand disease epidemics, and to design effective public health measures. Clustering and terminal branch lengths (TBL) analyses are commonly applied to genomic data sets of Mycobacterium tuberculosis (MTB) to identify sub-populations with increased transmission. Here, I used a simulation-based approach to investigate what epidemiological processes influence the results of clustering and TBL analyses, and whether differences in transmission can be detected with these methods. I simulated MTB epidemics with different dynamics (latency, infectious period, transmission rate, basic reproductive number R0, sampling proportion, sampling period, and molecular clock), and found that all considered factors, except for the length of the infectious period, affect the results of clustering and TBL distributions. I show that standard interpretations of this type of analyses ignore two main caveats: (1) clustering results and TBL depend on many factors that have nothing to do with transmission, (2) clustering results and TBL do not tell anything about whether the epidemic is stable, growing, or shrinking, unless all the additional parameters that influence these metrics are known, or assumed identical between sub-populations. An important consequence is that the optimal SNP threshold for clustering depends on the epidemiological conditions, and that sub-populations with different epidemiological characteristics should not be analyzed with the same threshold. Finally, these results suggest that different clustering rates and TBL distributions, that are found consistently between different MTB lineages, are probably due to intrinsic bacterial factors, and do not indicate necessarily differences in transmission or evolutionary success.
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spelling pubmed-92396812022-06-29 Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis Menardo, Fabrizio eLife Epidemiology and Global Health Detecting factors associated with transmission is important to understand disease epidemics, and to design effective public health measures. Clustering and terminal branch lengths (TBL) analyses are commonly applied to genomic data sets of Mycobacterium tuberculosis (MTB) to identify sub-populations with increased transmission. Here, I used a simulation-based approach to investigate what epidemiological processes influence the results of clustering and TBL analyses, and whether differences in transmission can be detected with these methods. I simulated MTB epidemics with different dynamics (latency, infectious period, transmission rate, basic reproductive number R0, sampling proportion, sampling period, and molecular clock), and found that all considered factors, except for the length of the infectious period, affect the results of clustering and TBL distributions. I show that standard interpretations of this type of analyses ignore two main caveats: (1) clustering results and TBL depend on many factors that have nothing to do with transmission, (2) clustering results and TBL do not tell anything about whether the epidemic is stable, growing, or shrinking, unless all the additional parameters that influence these metrics are known, or assumed identical between sub-populations. An important consequence is that the optimal SNP threshold for clustering depends on the epidemiological conditions, and that sub-populations with different epidemiological characteristics should not be analyzed with the same threshold. Finally, these results suggest that different clustering rates and TBL distributions, that are found consistently between different MTB lineages, are probably due to intrinsic bacterial factors, and do not indicate necessarily differences in transmission or evolutionary success. eLife Sciences Publications, Ltd 2022-06-28 /pmc/articles/PMC9239681/ /pubmed/35762734 http://dx.doi.org/10.7554/eLife.76780 Text en © 2022, Menardo https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://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
Menardo, Fabrizio
Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis
title Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis
title_full Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis
title_fullStr Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis
title_full_unstemmed Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis
title_short Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis
title_sort understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of mycobacterium tuberculosis
topic Epidemiology and Global Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239681/
https://www.ncbi.nlm.nih.gov/pubmed/35762734
http://dx.doi.org/10.7554/eLife.76780
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