Expression-Based Network Biology Identifies Alteration in Key Regulatory Pathways of Type 2 Diabetes and Associated RiskComplications 英文参考文献.docVIP

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Expression-Based Network Biology Identifies Alteration in Key Regulatory Pathways of Type 2 Diabetes and Associated RiskComplications 英文参考文献.doc

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Expression-Based Network Biology Identifies Alteration in Key Regulatory Pathways of Type 2 Diabetes and Associated RiskComplications 英文参考文献

Expression-BasedNetworkBiologyIdentifiesAlteration inKeyRegulatoryPathwaysofType2Diabetesand AssociatedRisk/Complications UrmiSengupta1,SanchaitaUkil1,NevenkaDimitrova3,ShipraAgrawal1,2* 1InstituteofBioinformaticsandAppliedBiotechnology,Bangalore,Karnataka,India,2BioCOSLifeSciencesPrivateLimited,Bangalore,Karnataka,India,3PhilipsResearch NorthAmerica,BriarcliffManor,NewYork,UnitedStatesofAmerica Abstract Type2diabetesmellitus(T2D)isamultifactorialandgeneticallyheterogeneousdiseasewhichleadstoimpairedglucose homeostasis and insulin resistance. The advanced form of disease causes acute cardiovascular, renal, neurological and microvascularcomplications.Thusthereisaconstantneedtodiscovernewandefficienttreatmentagainstthediseaseby seeking to uncover various novel alternate signalling mechanisms that can lead to diabetes and its associated complications. The present study allows detection of molecular targets by unravelling their role in altered biological pathwaysduringdiabetesanditsassociatedriskfactorsandcomplications.Wehaveusedanintegratedfunctionalnetworks conceptbymergingco-expressionnetworkandinteractionnetworktodetectthetranscriptionallyalteredpathwaysand regulations involved in the disease. Our analysis reports four novel significant networks which could lead to the developmentofdiabetesandotherassociateddysfunctions.(a)ThefirstnetworkillustratestheupregulationofTGFBRII facilitating oxidative stress and causing the expression of early transcription genes via MAPK pathway leading to cardiovascularandkidneyrelatedcomplications.(b)ThesecondnetworkdemonstratesnovelinteractionsbetweenGAPDH and inflammatory and proliferation candidate genes i.e., SUMO4 and EGFR indicating a new link between obesity and diabetes.(c)ThethirdnetworkportraysuniqueinteractionsPTPN1withEGFRandCAV1whichcouldleadtoanimpaired vascular function in diabetic nephropathy condition. (d) Lastly, from our fourth network we have inferred that the interaction of b-catenin with CDH5 and TGFBR1 through