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Identifying predictors of time-inhomogeneous viral evolutionary processes
- Source :
- Virus Evolution, Virus evolution, vol 2, iss 2
- Publication Year :
- 2016
- Publisher :
- Oxford University Press, 2016.
-
Abstract
- Various factors determine the rate at which mutations are generated and fixed in viral genomes. Viral evolutionary rates may vary over the course of a single persistent infection and can reflect changes in replication rates and selective dynamics. Dedicated statistical inference approaches are required to understand how the complex interplay of these processes shapes the genetic diversity and divergence in viral populations. Although evolutionary models accommodating a high degree of complexity can now be formalized, adequately informing these models by potentially sparse data, and assessing the association of the resulting estimates with external predictors, remains a major challenge. In this article, we present a novel Bayesian evolutionary inference method, which integrates multiple potential predictors and tests their association with variation in the absolute rates of synonymous and non-synonymous substitutions along the evolutionary history. We consider clinical and virological measures as predictors, but also changes in population size trajectories that are simultaneously inferred using coalescent modelling. We demonstrate the potential of our method in an application to within-host HIV-1 sequence data sampled throughout the infection of multiple patients. While analyses of individual patient populations lack statistical power, we detect significant evidence for an abrupt drop in non-synonymous rates in late stage infection and a more gradual increase in synonymous rates over the course of infection in a joint analysis across all patients. The former is predicted by the immune relaxation hypothesis while the latter may be in line with increasing replicative fitness during the asymptomatic stage. ispartof: Virus Evolution vol:2 issue:2 ispartof: location:England status: published
- Subjects :
- 0301 basic medicine
Bayesian probability
Inference
Bayesian phylogenetics
Biology
Microbiology
Statistical power
Coalescent theory
03 medical and health sciences
Virology
Statistical inference
codon substitution models
Genetics
virus evolution
Evolutionary Biology
Genetic diversity
Population size
generalized linear models
3. Good health
030104 developmental biology
Evolutionary biology
Viral evolution
evolutionary rate
epoch models
Research Article
pathogen
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Virus Evolution, Virus evolution, vol 2, iss 2
- Accession number :
- edsair.doi.dedup.....6a4b54a31b6921058e6a13310daf3908