title: Gene-wide identification of episodic selection.
abstract: We present BUSTED, a new approach to identifying gene-wide evidence of episodic positive selection, where the non-synonymous substitution rate is transiently greater than the synonymous rate. BUSTED can be used either on an entire phylogeny (without requiring an a priori hypothesis regarding which branches are under positive selection) or on a pre-specified subset of foreground lineages (if a suitable a priori hypothesis is available). Selection is modeled as varying stochastically over branches and sites, and we propose a computationally inexpensive evidence metric for identifying sites subject to episodic positive selection on any foreground branches. We compare BUSTED with existing models on simulated and empirical data. An implementation is available on www.datamonkey.org/busted, with a widget allowing the interactive specification of foreground branches.
authors.affiliation: Department of Medicine, University of California San Diego.
authors.forename: Ben
authors.initials: B
authors.lastname: Murrell
authors.affiliation: Department of Medicine, University of California San Diego.
authors.forename: Steven
authors.initials: S
authors.lastname: Weaver
authors.affiliation: Graduate program in Bioinformatics and Systems Biology, University of California San Diego.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of California San Diego.
authors.forename: Joel O
authors.initials: JO
authors.lastname: Wertheim
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA.
authors.forename: Sasha
authors.initials: S
authors.lastname: Murrell
authors.affiliation: Graduate program in Bioinformatics and Systems Biology, University of California San Diego.
authors.forename: Anthony
authors.initials: A
authors.lastname: Aylward
authors.affiliation: Graduate program in Bioinformatics and Systems Biology, University of California San Diego Graduate program in Biomedical Informatics, University of California San Diego.
authors.forename: Kemal
authors.initials: K
authors.lastname: Eren
authors.affiliation: Canyon Crest Academy, San Diego, CA.
authors.forename: Tristan
authors.initials: T
authors.lastname: Pollner
authors.affiliation: Computational Biology Group, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Darren P
authors.initials: DP
authors.lastname: Martin
authors.affiliation: Department of Medicine, University of California San Diego Veterans Affairs San Diego Healthcare System, San Diego, CA.
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of California San Diego Department of Mathematical Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Konrad
authors.initials: K
authors.lastname: Scheffler
authors.affiliation: Department of Medicine, University of California San Diego spond@ucsd.edu.
authors.forename: Sergei L
authors.initials: SL
authors.lastname: Kosakovsky Pond
mesh_terms: D003198:Computer Simulation; D019143:Evolution, Molecular; D008957:Models, Genetic; D010802:Phylogeny; D012641:Selection, Genetic / Q000235:genetics*
keywords: branch-site model; episodic selection; evolutionary model; random effects model