DMCA
Fast pairwise structural RNA alignments by pruning of the dynamical programming matrix. PLoS Comput Biol 3 (2007)
| Citations: | 42 - 6 self |
BibTeX
@MISC{Havgaard07fastpairwise,
author = {Jakob H. Havgaard and Elfar Torarinsson and Jan Gorodkin},
title = {Fast pairwise structural RNA alignments by pruning of the dynamical programming matrix. PLoS Comput Biol 3},
year = {2007}
}
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Abstract
It has become clear that noncoding RNAs (ncRNA) play important roles in cells, and emerging studies indicate that there might be a large number of unknown ncRNAs in mammalian genomes. There exist computational methods that can be used to search for ncRNAs by comparing sequences from different genomes. One main problem with these methods is their computational complexity, and heuristics are therefore employed. Two heuristics are currently very popular: pre-folding and pre-aligning. However, these heuristics are not ideal, as pre-aligning is dependent on sequence similarity that may not be present and pre-folding ignores the comparative information. Here, pruning of the dynamical programming matrix is presented as an alternative novel heuristic constraint. All subalignments that do not exceed a length-dependent minimum score are discarded as the matrix is filled out, thus giving the advantage of providing the constraints dynamically. This has been included in a new implementation of the FOLDALIGN algorithm for pairwise local or global structural alignment of RNA sequences. It is shown that time and memory requirements are dramatically lowered while overall performance is maintained. Furthermore, a new divide and conquer method is introduced to limit the memory requirement during global alignment and backtrack of local alignment. All branch points in the computed RNA structure are found and used to divide the structure into smaller unbranched segments. Each segment is then realigned and backtracked in a normal fashion. Finally, the FOLDALIGN algorithm has also been updated with a better memory implementation and an improved energy model. With these improvements in the algorithm, the FOLDALIGN software package provides the molecular biologist with an efficient and user-friendly tool for searching for new ncRNAs. The software package is available for download at
Keyphrases
dynamical programming matrix plo comput biol fast pairwise structural rna alignment memory requirement foldalign algorithm local alignment unbranched segment comparative information large number main problem unknown ncrnas global structural alignment branch point mammalian genome user-friendly tool different genome software package improved energy model conquer method new ncrnas computational method foldalign software package memory implementation length-dependent minimum score normal fashion computed rna structure new implementation molecular biologist overall performance sequence similarity computational complexity play important role rna sequence new divide pre-folding ignores alternative novel heuristic constraint global alignment
