accurate reconstruction of insertion-deletion histories by statistical phylogenetics通过统计系统发生学准确重建insertion-deletion历史.pdfVIP

Accurate Reconstruction of Insertion-Deletion Histories by Statistical Phylogenetics 1 2 3 1 Oscar Westesson , Gerton Lunter , Benedict Paten , Ian Holmes * 1 University of California Berkeley and University of California San Francisco Graduate Program in Bioengineering, University of California, Berkeley, California, United States of America, 2 Wellcome Trust Center for Human Genetics, Oxford, Oxford, United Kingdom, 3 Baskin School of Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America 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 gene