Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases 英文参考文献.docVIP

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Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases 英文参考文献.doc

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Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases 英文参考文献

Disease-AgingNetworkRevealsSignificantRolesof AgingGenesinConnectingGeneticDiseases JiguangWang1,2,ShihuaZhang1,YongWang1,LuonanChen3,4*,Xiang-SunZhang1* 1AcademyofMathematicsandSystemsScience,ChineseAcademyofSciences,Beijing,China,2GraduateSchooloftheChineseAcademyofSciences,Beijing,China, 3InstituteofSystemsBiology,ShanghaiUniversity,Shanghai,China,4DepartmentofElectricalEngineeringandElectronics,OsakaSangyoUniversity,Osaka,Japan Abstract One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recentstudiessuggestthattherelationshipbetweengeneticdiseasesandtheagingprocessisimportantinunderstanding themolecular mechanisms of complex diseases. Although some intricate associations havebeeninvestigated for along time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationshipamongaginggenesandgeneticdiseasegenes.Specifically,weintegratehumanprotein-proteininteractions (PPIs), disease-gene associations, aging-gene associations, and physiological system–based genetic disease classification informationinasinglegraph-theoreticframeworkandfindthat(1)humandiseasegenesaremuchclosertoaginggenes thanexpectedbychance;and(2)diseasescanbecategorizedintotwotypesaccordingtotheirrelationshipswithaging. TypeIdiseaseshavetheirgenessignificantlyclosetoaginggenes,whiletypeIIdiseasesdonot.Furthermore,weexamine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genesoftypeIdiseasesareinacentralpositionofaPPInetworkwhiletypeIIarenot;(3)moreimportantly,wedefinean asymmetricclosenessbasedonthePPInetworktodescriberelationshipsbetweendiseases,andfindthataginggenesmake a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network- basedstudyprovidesnotonlyevidencefortheintricaterelationshipbetweentheagingprocessandgeneticdiseases,but alsobi