Modeling the growth and decline of pathogen effective population size provides insight into epidemic dynamics and drivers of antimicrobial resistance
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Author(s)
Volz, E
Didelot, Xavier
Type
Journal Article
Abstract
Nonparametric population genetic modeling provides a simple and flexible approach for studying demographic history and epidemic dynamics using pathogen sequence data. Existing Bayesian approaches are premised on stochastic processes with stationary increments which may provide an unrealistic prior for epidemic histories which feature extended period of exponential growth or decline. We show that nonparametric models defined in terms of the growth rate of the effective population size can provide a more realistic prior for epidemic history. We propose a nonparametric autoregressive model on the growth rate as a prior for effective population size, which corresponds to the dynamics expected under many epidemic situations. We demonstrate the use of this model within a Bayesian phylodynamic inference framework. Our method correctly reconstructs trends of epidemic growth and decline from pathogen genealogies even when genealogical data are sparse and conventional skyline estimators erroneously predict stable population size. We also propose a regression approach for relating growth rates of pathogen effective population size and time-varying variables that may impact the replicative fitness of a pathogen. The model is applied to real data from rabies virus and Staphylococcus aureus epidemics. We find a close correspondence between the estimated growth rates of a lineage of methicillin-resistant S. aureus and population-level prescription rates of
β
-lactam antibiotics. The new models are implemented in an open source R package called skygrowth which is available at https://github.com/mrc-ide/skygrowth.
β
-lactam antibiotics. The new models are implemented in an open source R package called skygrowth which is available at https://github.com/mrc-ide/skygrowth.
Date Issued
2018-07-01
Date Acceptance
2018-02-07
Citation
Systematic Biology, 2018, 67 (4), pp.719-728
ISSN
1063-5157
Publisher
Oxford University Press (OUP)
Start Page
719
End Page
728
Journal / Book Title
Systematic Biology
Volume
67
Issue
4
Copyright Statement
© The Author(s) 2018. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/
4.0/), which permits
unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For Permissions, please email: jou
rnals.permissions@oup.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/
4.0/), which permits
unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For Permissions, please email: jou
rnals.permissions@oup.com
Sponsor
Medical Research Council (MRC)
National Institutes of Health
Grant Number
MR/K010174/1B
258162IMP
Subjects
MRSA
antimicrobial resistance
effective population size
growth rate
phylodynamics
skygrowth
0603 Evolutionary Biology
0604 Genetics
Evolutionary Biology
Publication Status
Published
Date Publish Online
2018-02-07