title: Using mixtures of common ancestors for estimating the probabilities of discrete events in biological sequences.
abstract: Accurately estimating probabilities from observations is important for probabilistic-based approaches to problems in computational biology. In this paper we present a biologically-motivated method for estimating probability distributions over discrete alphabets from observations using a mixture model of common ancestors. The method is an extension of substitution matrix-based probability estimation methods. In contrast to previous such methods, our method has a simple Bayesian interpretation and has the advantage over Dirichlet mixtures that it is both effective and simple to compute for large alphabets. The method is applied to estimate amino acid probabilities based on observed counts in an alignment and is shown to perform comparably to previous methods. The method is also applied to estimate probability distributions over protein families and improves protein classification accuracy.
authors.affiliation: Department of Computer Science, Columbia University, New York, NY, 10027, USA. eeskin@cs.columbia.edu
authors.forename: E
authors.initials: E
authors.lastname: Eskin
authors.forename: W N
authors.initials: WN
authors.lastname: Grundy
authors.forename: Y
authors.initials: Y
authors.lastname: Singer
mesh_terms: D000595:Amino Acid Sequence; D001499:Bayes Theorem; D019295:Computational Biology; D019143:Evolution, Molecular; D008957:Models, Genetic; D011336:Probability; D011506:Proteins / Q000235:genetics; D016415:Sequence Alignment / Q000706:statistics & numerical data*
chemical_list: D011506:Proteins