Partitioning of Minimotifs Based on Function with Improved Prediction Accuracy 英文参考文献.docVIP

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Partitioning of Minimotifs Based on Function with Improved Prediction Accuracy 英文参考文献.doc

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Partitioning of Minimotifs Based on Function with Improved Prediction Accuracy 英文参考文献

PartitioningofMinimotifsBasedonFunctionwith ImprovedPredictionAccuracy SanguthevarRajasekaran1*.,TianMi1.,JerlinCamilusMerlin1,AaronOommen1,PatrickGradie2, MartinR.Schiller2* 1Department of Computer Science and Engineering, University of Connecticut, Storrs, Connecticut, United States of America, 2School of Life Sciences, University of NevadaLasVegas,LasVegas,Nevada,UnitedStatesofAmerica Abstract Background:Minimotifsareshortcontiguouspeptidesequencesinproteinsthatareknowntohaveafunctioninatleast oneotherprotein.Oneoftheprincipallimitationsinminimotifpredictionisthatfalsepositiveslimittheusefulnessofthis approach.Asasteptowardresolvingthisproblemwehavebuilt,implemented,andtestedanewdata-drivenalgorithm thatreducesfalse-positivepredictions. Methodology/Principal Findings: Certain domains and minimotifs are known to be strongly associated with a known cellularprocessormolecularfunction.Therefore,wehypothesizedthatbyrestrictingminimotifpredictionstothosewhere theminimotifcontainingproteinandtargetproteinhavearelatedcellularormolecularfunction,thepredictionismore likelytobeaccurate.ThisfilterwasimplementedinMinimotifMinerusingfunctionannotationsfromtheGeneOntology. We have also combined two filters that are based on entirely different principles and this combined filter has a better predictabilitythantheindividualcomponents. Conclusions/Significance: Testing these functional filters on known and random minimotifs has revealed that they are capableofseparatingtruemotifsfromfalsepositives.Inparticular,forthecellularfunctionfilter,thepercentageofknown minimotifsthatarenotremovedbythefilteris,4.6timesthatofrandomminimotifs.Forthemolecularfunctionfilterthis ratiois,2.9.Theseresults,togetherwiththecomparisonwiththepublishedfrequencyscorefilter,stronglysuggestthat the new filters differentiate true motifs from random background with good confidence. A combination of the function filtersandthefrequencyscorefilterperformsbetterthanthesetwoindividualfilters. Citation:RajasekaranS