Novel Protein-Protein Interactions Inferred from Literature Context 英文参考文献.docVIP

NovelProtein-ProteinInteractionsInferredfrom LiteratureContext HermanH.H.B.M.vanHaagen1*,PeterA.C.’tHoen1,AlessandroBotelhoBovo2,AntoinedeMorre′e1, ErikM.vanMulligen1,ChristineChichester1,JanA.Kors1,JohanT.denDunnen1,Gert-JanB.van Ommen1,Silve`reM.vanderMaarel1,Vin?′ciusMedinaKern2,BarendMons1,MartijnJ.Schuemie1 1Biosemantics Association, Department of Human Genetics, Leiden University Medical Center, Leiden, and Department of Medical Informatics, Erasmus University MedicalCenter,Rotterdam,TheNetherlands,2Post-GraduatePrograminKnowledgeEngineeringandManagement(EGC),FederalUniversityofSantaCatarina(UFSC), Floriano′polis,Brazil Abstract We have developed a method that predicts Protein-Protein Interactions (PPIs) based on the similarity of the context in whichproteinsappearinliterature.ThismethodoutperformspreviouslydevelopedPPIpredictionalgorithmsthatrelyon theconjunctionoftwoproteinnamesinMEDLINEabstracts.Weshowsignificantincreasesincoverage(76%versus32%) andsensitivity(66%versus41%ataspecificityof95%)forthepredictionofPPIscurrentlyarchivedin6PPIdatabases.A retrospective analysis shows that PPIs can efficiently be predicted before they enter PPI databases and before their interactionisexplicitlydescribedintheliterature.ThepracticalvalueofthemethodfordiscoveryofnovelPPIsisillustrated by the experimental confirmation of the inferred physical interaction between CAPN3 and PARVB, which was based on frequentco-occurrenceofbothproteinswithconceptslikeZ-disc,dysferlin,andalpha-actinin.Therelationshipsbetween proteinspredictedbyourmethodarebroaderthanPPIs,andincludeproteinsinthesamecomplexorpathway.Dependent onthetypeofrelationshipsdeemeduseful,theprecisionofourmethodcanbeashighas90%.Thefullsetofpredicted interactionsisavailableinadownloadablematrixandthroughthewebtoolNermal,whichliststhemostlikelyinteraction partners for a given protein. Our framework can be used for prioritizing potential interaction partners, hitherto undiscovered,forfollow-upstudiesandtoaidthegeneratio