title: Detecting and Quantifying Changing Selection Intensities from Time-Sampled Polymorphism Data.
abstract: During his well-known debate with Fisher regarding the phenotypic dataset of Panaxia dominula, Wright suggested fluctuating selection as a potential explanation for the observed change in allele frequencies. This model has since been invoked in a number of analyses, with the focus of discussion centering mainly on random or oscillatory fluctuations of selection intensities. Here, we present a novel method to consider nonrandom changes in selection intensities using Wright-Fisher approximate Bayesian (ABC)-based approaches, in order to detect and evaluate a change in selection strength from time-sampled data. This novel method jointly estimates the position of a change point as well as the strength of both corresponding selection coefficients (and dominance for diploid cases) from the allele trajectory. The simulation studies of this method reveal the combinations of parameter ranges and input values that optimize performance, thus indicating optimal experimental design strategies. We apply this approach to both the historical dataset of P. dominula in order to shed light on this historical debate, as well as to whole-genome time-serial data from influenza virus in order to identify sites with changing selection intensities in response to drug treatment.
authors: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: Hyunjin
authors: 0000-0002-7052-0971
authors: H
authors: Shim
authors: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: Stefan
authors: S
authors: Laurent
authors: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: Sebastian
authors: S
authors: Matuszewski
authors: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland International Agency for Research on Cancer, Lyon, France.
authors: Matthieu
authors: M
authors: Foll
authors: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: Jeffrey D
authors: JD
authors: Jensen
mesh_terms: D000465:Algorithms; D000483:Alleles; D001499:Bayes Theorem; D005075:Biological Evolution; D003198:Computer Simulation; D005828:Genetics, Population; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D008957:Models, Genetic; D009154:Mutation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D012641:Selection, Genetic
keywords: Wright-Fisher model; approximate Bayesian computation; change point analysis; fluctuating selection; time-sampled data