SimulFold Simultaneously Inferring RNA Structures Including Pseudoknots, Alignments, and Trees Using a Bayesian MCMC Framework 英文参考文献.docVIP

SimulFold:SimultaneouslyInferringRNA StructuresIncludingPseudoknots,Alignments, andTreesUsingaBayesianMCMCFramework Irmtraud M.Meyer1,2*,Istva′nMiklo′s3,4,5 1 UBC Bioinformatics Centre, University of British Columbia, Vancouver, British Columbia, Canada, 2 Department of Computer Science, University of British Columbia, Vancouver,BritishColumbia,Canada,3Alfre′d Re′nyiInstituteofMathematics,HungarianAcademyofSciences,Budapest,Hungary,4ComputerandAutomationResearch Institute(MTA-SZTAKI),HungarianAcademyofSciences,Budapest,Hungary,5eScienceRegionalKnowledgeCentre,Eo¨tvo¨sLora′nd University,Budapest,Hungary Computational methods for predicting evolutionarily conserved rather than thermodynamic RNA structures have recentlyattractedincreasedinterest.Thesemethodsareindispensablenotonlyforelucidatingtheregulatoryrolesof knownRNAtranscripts,butalsoforpredictingRNAgenes.Ithasbeennotoriouslydifficulttodevisethemtomakethe best use of the available data and to predict high-quality RNA structures that may also contain pseudoknots. We introduce a novel theoretical framework for co-estimating an RNA secondary structure including pseudoknots, a multiple sequence alignment, and an evolutionary tree, given several RNA input sequences. We also present an implementationoftheframeworkinanewcomputerprogram,calledSimulFold,whichemploysaBayesianMarkov chainMonteCarlomethodtosamplefromthejointposteriordistributionofRNAstructures,alignments,andtrees.We use the new framework to predict RNA structures, and comprehensively evaluate the quality of our predictions by comparing our results to those of several other programs. We also present preliminary data that show SimulFold’s potentialasanalignmentandphylogenypredictionmethod.SimulFoldovercomesmanyconceptuallimitationsthat current RNA structure prediction methods face, introduces several new theoretical techniques, and generates high- qualitypredictionsofconservedRNAstructuresthatmayincludepseudoknots.Itisthuslikelytohaveastrongimpact