Bayesian Inference of Clonal Expansions in a Dated Phylogeny

Author:

Helekal David1,Ledda Alice2,Volz Erik3ORCID,Wyllie David4,Didelot Xavier5ORCID

Affiliation:

1. Centre for Doctoral Training in Mathematics for Real-World Systems, University of Warwick, Coventry CV47AL, UK

2. Healthcare Associated Infections and Antimicrobial Resistance Division, National Infection Service, Public Health England, London NW95EQ, UK

3. Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W21PG, UK

4. Field Service, East of England, National Infection Service, Public Health England, Cambridge CB20SR, UK

5. School of Life Sciences and Department of Statistics, University of Warwick, Coventry CV47AL, UK

Abstract

Abstract Microbial population genetics models often assume that all lineages are constrained by the same population size dynamics over time. However, many neutral and selective events can invalidate this assumption and can contribute to the clonal expansion of a specific lineage relative to the rest of the population. Such differential phylodynamic properties between lineages result in asymmetries and imbalances in phylogenetic trees that are sometimes described informally but which are difficult to analyze formally. To this end, we developed a model of how clonal expansions occur and affect the branching patterns of a phylogeny. We show how the parameters of this model can be inferred from a given dated phylogeny using Bayesian statistics, which allows us to assess the probability that one or more clonal expansion events occurred. For each putative clonal expansion event, we estimate its date of emergence and subsequent phylodynamic trajectory, including its long-term evolutionary potential which is important to determine how much effort should be placed on specific control measures. We demonstrate the applicability of our methodology on simulated and real data sets. Inference under our clonal expansion model can reveal important features in the evolution and epidemiology of infectious disease pathogens. [Clonal expansion; genomic epidemiology; microbial population genomics; phylodynamics.]

Funder

UK Engineering and Physical Sciences Research Council

EPSRC Centre for Doctoral Training in Mathematics for Real-World Systems II

National Institute for Health Research

Health Protection Research Unit in Genomics and Enabling Data

Publisher

Oxford University Press (OUP)

Subject

Genetics,Ecology, Evolution, Behavior and Systematics

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