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Statistical Applications in Genetics and Molecular Biology

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A Heuristic Bayesian Method for Segmenting DNA Sequence Alignments and Detecting Evidence for Recombination and Gene Conversion

Anna Kedzierska1 / Dirk Husmeier2

1Wroclaw University of Technology, Poland

2Biomathematics and Statistics Scotland (BioSS), United Kingdom

Citation Information: Statistical Applications in Genetics and Molecular Biology. Volume 5, Issue 1, ISSN (Online) 1544-6115, DOI: 10.2202/1544-6115.1238, October 2006

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We propose a heuristic approach to the detection of evidence for recombination and gene conversion in multiple DNA sequence alignments. The proposed method consists of two stages. In the first stage, a sliding window is moved along the DNA sequence alignment, and phylogenetic trees are sampled from the conditional posterior distribution with MCMC. To reduce the noise intrinsic to inference from the limited amount of data available in the typically short sliding window, a clustering algorithm based on the Robinson-Foulds distance is applied to the trees thus sampled, and the posterior distribution over tree clusters is obtained for each window position. While changes in this posterior distribution are indicative of recombination or gene conversion events, it is difficult to decide when such a change is statistically significant. This problem is addressed in the second stage of the proposed algorithm, where the distributions obtained in the first stage are post-processed with a Bayesian hidden Markov model (HMM). The emission states of the HMM are associated with posterior distributions over phylogenetic tree topology clusters. The hidden states of the HMM indicate putative recombinant segments. Inference is done in a Bayesian sense, sampling parameters from the posterior distribution with MCMC. Of particular interest is the determination of the number of hidden states as an indication of the number of putative recombinant regions. To this end, we apply reversible jump MCMC, and sample the number of hidden states from the respective posterior distribution.

Keywords: DNA sequence alignment; phylogenetics; interspecific recombination; moving window method; probabilistic divergence measure; hidden Markov model; model selection; Bayesian inference; reversible jump Markov chain Monte Carlo

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