title: Accurate reconstruction of insertion-deletion histories by statistical phylogenetics.
abstract: The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.
authors.affiliation: University of California Berkeley and University of California San Francisco Graduate Program in Bioengineering, University of California, Berkeley, California, United States of America.
authors.forename: Oscar
authors.initials: O
authors.lastname: Westesson
authors.forename: Gerton
authors.initials: G
authors.lastname: Lunter
authors.forename: Benedict
authors.initials: B
authors.lastname: Paten
authors.forename: Ian
authors.initials: I
authors.lastname: Holmes
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D019143:Evolution, Molecular; D006801:Humans; D054643:INDEL Mutation; D016013:Likelihood Functions; D008390:Markov Chains; D008957:Models, Genetic; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D016415:Sequence Alignment