Background: Non-coding DNA sequences comprise a very large proportion of the total genomic content of mammals, most other vertebrates, many invertebrates, and most plants. Unraveling the functional significance of non-coding DNA depends on how well we are able to align non-coding DNA sequences. However, the alignment of non-coding DNA sequences is more difficult than aligning protein-coding sequences. Results: Here we present an improved pair-hidden-Markov-Model (pair HMM) based method for performing global pairwise alignment of non-coding DNA sequences. The method uses an explicit model of indel length frequency distribution which can be specified, and allows any time reversible model of nucleotide substitution. The method uses a deterministic global optimiser to find the alignment with the highest posterior probability. We test MCALIGN2 in simulations, and compare it to a previous Monte Carlo based method (MCALIGN), to the pair HMM method of Knudsen and Miyamoto, and to a heuristic ...
Jun Wang, Peter D. Keightley, Toby Johnson