Exact calculation of distributions on integers, with application to sequence alignment.

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
Lee A Newberg, Charles E Lawrence

Abstract

Computational biology is replete with high-dimensional discrete prediction and inference problems. Dynamic programming recursions can be applied to several of the most important of these, including sequence alignment, RNA secondary-structure prediction, phylogenetic inference, and motif finding. In these problems, attention is frequently focused on some scalar quantity of interest, a score, such as an alignment score or the free energy of an RNA secondary structure. In many cases, score is naturally defined on integers, such as a count of the number of pairing differences between two sequence alignments, or else an integer score has been adopted for computational reasons, such as in the test of significance of motif scores. The probability distribution of the score under an appropriate probabilistic model is of interest, such as in tests of significance of motif scores, or in calculation of Bayesian confidence limits around an alignment. Here we present three algorithms for calculating the exact distribution of a score of this type; then, in the context of pairwise local sequence alignments, we apply the approach so as to find the alignment score distribution and Bayesian confidence limits.

References

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Nov 1, 2008·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Lee A Newberg

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Citations

Feb 9, 2012·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Michiaki Hamada, Kiyoshi Asai
Mar 1, 2012·Briefings in Bioinformatics·Ting HuangZengyou He
May 30, 2009·Bioinformatics·Theo A KnijnenburgIlya Shmulevich
Jul 27, 2011·Bioinformatics·Donglai WeiCharles E Lawrence
Sep 17, 2010·Nucleic Acids Research·Michiaki HamadaKiyoshi Asai
Feb 11, 2010·BMC Bioinformatics·Martin C FrithPaul Horton
Jun 28, 2013·Briefings in Bioinformatics·Michiaki Hamada
Jan 19, 2016·Trends in Ecology & Evolution·August GuangCasey W Dunn
Sep 29, 2011·Journal of Theoretical Biology·Guillermo Peris, Andrés Marzal
Sep 2, 2010·Genome Research·Paul MedvedevMichael Brudno

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