title: Statistical alignment: computational properties, homology testing and goodness-of-fit.
abstract: The model of insertions and deletions in biological sequences, first formulated by Thorne, Kishino, and Felsenstein in 1991 (the TKF91 model), provides a basis for performing alignment within a statistical framework. Here we investigate this model.Firstly, we show how to accelerate the statistical alignment algorithms several orders of magnitude. The main innovations are to confine likelihood calculations to a band close to the similarity based alignment, to get good initial guesses of the evolutionary parameters and to apply an efficient numerical optimisation algorithm for finding the maximum likelihood estimate. In addition, the recursions originally presented by Thorne, Kishino and Felsenstein can be simplified. Two proteins, about 1500 amino acids long, can be analysed with this method in less than five seconds on a fast desktop computer, which makes this method practical for actual data analysis.Secondly, we propose a new homology test based on this model, where homology means that an ancestor to a sequence pair can be found finitely far back in time. This test has statistical advantages relative to the traditional shuffle test for proteins.Finally, we describe a goodness-of-fit test, that allows testing the proposed insertion-deletion (indel) process inherent to this model and find that real sequences (here globins) probably experience indels longer than one, contrary to what is assumed by the model.
authors.affiliation: Department of Genetics and Ecology The Institute of Biological Science, University of Aarhus, Building 540, Ny Munkegade, Arhus C, 8000, Denmark. jotun.hein@biology.au.dk
authors.forename: J
authors.initials: J
authors.lastname: Hein
authors.forename: C
authors.initials: C
authors.lastname: Wiuf
authors.forename: B
authors.initials: B
authors.lastname: Knudsen
authors.forename: M B
authors.initials: MB
authors.lastname: Møller
authors.forename: G
authors.initials: G
authors.lastname: Wibling
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D005914:Globins / Q000737:chemistry*; D006801:Humans; D016013:Likelihood Functions; D008969:Molecular Sequence Data; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D012984:Software; D013997:Time Factors
chemical_list: D005914:Globins