Fast Pairwise Structural RNA Alignments by Pruning of the Dynamical Programming Matrix 英文参考文献.docVIP

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Fast Pairwise Structural RNA Alignments by Pruning of the Dynamical Programming Matrix 英文参考文献.doc

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Fast Pairwise Structural RNA Alignments by Pruning of the Dynamical Programming Matrix 英文参考文献

FastPairwiseStructuralRNAAlignmentsby PruningoftheDynamicalProgrammingMatrix Jakob H.Havgaard1,Elfar Torarinsson1,2,Jan Gorodkin1* 1DivisionofGeneticsandBioinformatics,UniversityofCopenhagen,Frederiksberg,Denmark,2DepartmentofNaturalSciences,UniversityofCopenhagen,Frederiksberg, Denmark 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 thesemethodsistheircomputationalcomplexity,andheuristicsarethereforeemployed.Twoheuristicsarecurrently verypopular: pre-foldingandpre-aligning.However,theseheuristicsarenotideal,aspre-aligningisdependent on sequencesimilarity thatmaynotbepresentandpre-foldingignores thecomparative information.Here,pruningof thedynamical programmingmatrixispresentedasanalternativenovel heuristicconstraint.Allsubalignmentsthat do not exceed a length-dependent minimum score are discarded as the matrix is filled out, thus giving the advantageofprovidingtheconstraintsdynamically.Thishasbeenincludedinanewimplementationofthe 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.AllbranchpointsinthecomputedRNAstructurearefoundandusedtodividethestructureintosmaller unbranched segments. Each segment is then realigned and backtracked in a normal fashion. Finally, the FOLDALIGN algorithmhasalsobeenupdatedwithabettermemoryimplementationandanimprovedenergymodel.Withthese improvementsinthealgorithm,the FOLDALIGN softwarepackageprovidesthemolecularbiologistwithanefficientand