Using mixtures of common ancestors for estimating the probabilities of discrete events in biological sequences

Eleazar Eskin, William Noble Grundy and Yoram Singer

Proceedings of the Ninth International Conference on Intelligent Systems for Molecular Biology. July 21-25, 2001. To appear.


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 contract to previous substition matrix-based methods, our method has a simple Bayesian interpretation. The method presented in this paper 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 estimated probability distributions over protein families and improves protein classification accuracy.
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