Combining phylogenetic and hidden Markov models in biosequence analysis
RECOMB '03 Proceedings of the seventh annual international conference on Research in computational molecular biology
Genetic algorithms for the imitation of genomic styles in protein back translation
Theoretical Computer Science - Discrete applied problems, florilegium for E. Goles
Analysis of DNA sequence transformations on grids
Journal of Parallel and Distributed Computing
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We introduce a model of DNA sequence evolution which can account for biases in mutation rates that depend on the identity of the neighboring bases. An analytic solution for this class of models is developed by adopting well-known methods of nonlinear dynamics. Results are presented for the CpG-methylation-deamination process which dominates point substitutions in vertebrates. The dinucleotide frequencies generated by the model (using empirically obtained mutation rates) match the overall pattern observed in non-coding DNA. A web-based tool has been constructed to compute single- and dinucleotide frequencies for arbitrary neighbor-dependent mutation rates. Also provided is the backward procedure to infer the mutation rates using maximum likelihood analysis given the observed single- and dinucleotide frequencies. Reasonable estimates of the mutation rates can be obtained very efficiently, using generic non-coding DNA sequences as input, after masking out long homonucleotide subsequences. Our method is much more convenient and versatile to use than the traditional method of deducing mutation rates by counting mutation events in carefully chosen sequences. More generally, our approach provides a more realistic but still tractable description of non-coding genomic DNA, and may be used as a null model for various sequence analysis applications.