Ranking Candidate Disease Genes from Gene Expression and Protein Interaction A Katz-Centrality Based Approach 英文参考文献.docVIP

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Ranking Candidate Disease Genes from Gene Expression and Protein Interaction A Katz-Centrality Based Approach 英文参考文献.doc

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Ranking Candidate Disease Genes from Gene Expression and Protein Interaction A Katz-Centrality Based Approach 英文参考文献

RankingCandidateDiseaseGenesfromGeneExpression andProteinInteraction:AKatz-CentralityBased Approach JingZhao1,5*,Ting-HongYang1,YongxuHuang2,PetterHolme3,4,5* 1DepartmentofMathematics,LogisticalEngineeringUniversity,Chongqing,China,2DepartmentofHealthPolicyManagement,UniversityofPittsburgh,Pittsburgh, Pennsylvania,UnitedStatesofAmerica,3IceLab,DepartmentofPhysics,Umea? University,Umea?, Sweden,4DepartmentofEnergyScience,SungkyunkwanUniversity, Suwon,Korea,5KavliInstituteforTheoreticalPhysicsChina(KITPC),ChineseAcademyofSciences,Beijing,China Abstract Manydiseaseshavecomplexgeneticcauses, whereasetofallelescanaffectthepropensity ofgettingthedisease.The identificationofsuchdiseasegenesisimportanttounderstandthemechanisticandevolutionaryaspectsofpathogenesis, improve diagnosis and treatment of the disease, and aid in drug discovery. Current genetic studies typically identify chromosomalregionsassociatedspecificdiseases.Butpickingoutanunknowndiseasegenefromhundredsofcandidates located on the same genomic interval is still challenging. In this study, we propose an approach to prioritize candidate genes by integrating data of gene expression level, protein-protein interaction strength and known disease genes. Our methodisbasedonlyontwo,simple,biologicallymotivatedassumptions—thatageneisagooddisease-genecandidateif it is differentially expressed in cases and controls, or that it is close to other disease-gene candidates in its protein interaction network.We tested our methodon 40diseases in58 gene expressiondatasets ofthe NCBI GeneExpression Omnibus database. On these datasets our method is able to predict unknown disease genes as well as identifying pleiotropicgenesinvolvedinthephysiologicalcellularprocessesofmanydiseases.Ourstudynotonlyprovidesaneffective algorithmforprioritizingcandidatediseasegenesbutisalsoawaytodiscoverphenotypicinterdependency,cooccurrence andsharedpathophysiologybetweendifferentdisorders. Citation:ZhaoJ,YangT-H,HuangY,HolmeP(2011)Ranki