Functional Annotation and Identification of Candidate Disease Genes by Computational Analysis of Normal Tissue Gene Expression Data 英文参考文献.docVIP

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Functional Annotation and Identification of Candidate Disease Genes by Computational Analysis of Normal Tissue Gene Expression Data 英文参考文献.doc

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Functional Annotation and Identification of Candidate Disease Genes by Computational Analysis of Normal Tissue Gene Expression Data 英文参考文献

FunctionalAnnotationandIdentificationofCandidate DiseaseGenesbyComputationalAnalysisofNormal TissueGeneExpressionData LauraMiozzi1,RosarioMichaelPiro2,FabioRosa3,UgoAla2,LorenzoSilengo2,FerdinandoDiCunto2, PaoloProvero2* 1InstituteofPlantVirology,CNR,Turin,Italy,2MolecularBiotechnologyCenterandDepartmentofGenetics,BiologyandBiochemistry,UniversityofTurin,Torino,Italy, 3ISIFoundation,Turin,Italy Abstract Background:High-throughputgeneexpressiondatacanpredictgenefunctionthroughthe‘‘guiltbyassociation’’principle: coexpressedgenesarelikelytobefunctionallyassociated. Methodology/PrincipalFindings:Weanalyzedpubliclyavailableexpressiondataonnormalhumantissues.Theanalysisis basedontheintegrationofdataobtainedwithtwoexperimentalplatforms(microarraysandSAGE)andofvariousmeasures of dissimilarity between expression profiles. The building blocks of the procedure are the Ranked Coexpression Groups (RCG), small sets of tightly coexpressed genes which are analyzed in terms of functional annotation. Functionally characterizedRCGsareselectedbymeansofthemajorityruleandusedtopredictnewfunctionalannotations.Functionally characterized RCGs are enriched in groups of genes associated to similar phenotypes. We exploit this fact to find new candidatediseasegenesformanyOMIMphenotypesofunknownmolecularorigin. Conclusions/Significance:Wepredictnewfunctionalannotationsformanyhumangenes,showingthattheintegrationof differentdatasetsandcoexpressionmeasuressignificantlyimprovesthescopeoftheresults.Combininggeneexpression data, functional annotation and known phenotype-gene associations we provide candidate genes for several genetic diseasesofunknownmolecularbasis. Citation:MiozziL,PiroRM,RosaF,AlaU,SilengoL,etal.(2008)FunctionalAnnotationandIdentificationofCandidateDiseaseGenesbyComputationalAnalysis ofNormalTissueGeneExpressionData.PLoSONE3(6):e2439.doi:10.1371/journal.pone.0002439 Editor:OliverHofmann,HarvardSchoolofPublicHealth,UnitedStatesofAmerica ReceivedFebruary7,2008;AcceptedApril24,2008;Pub