Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions 英文参考文献.docVIP

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Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions 英文参考文献.doc

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Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions 英文参考文献

DifferentiallyExpressedRNAfromPublicMicroarray DataIdentifiesSerumProteinBiomarkersforCross- OrganTransplantRejectionandOtherConditions RongChen1,2,TaraK.Sigdel1,2,LiLi1,2,NeerajaKambham3,JoelT.Dudley1,2,Szu-chuanHsieh1,2 , R.BryanKlassen1,2,AmeryChen1,2,TuyenCaohuu4,AlexanderA.Morgan1,2,HannahA.Valantine4, KiranK.Khush4,MinnieM.Sarwal1,2*,AtulJ.Butte1,2 * 1DepartmentofPediatrics,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica,2LucilePackardChildren’sHospital,PaloAlto,California, UnitedStatesofAmerica,3DepartmentofPathology,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica,4DivisionofCardiovascular Medicine,DepartmentofMedicine,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica Abstract Serumproteinsareroutinelyusedtodiagnosediseases,butarehardtofindduetolowsensitivityinscreeningtheserum proteome. Public repositories of microarray data, such as the Gene Expression Omnibus (GEO), contain RNA expression profilesformorethan16,000biologicalconditions,coveringmorethan30%ofUnitedStatesmortality.Wehypothesized thatgenescodingforserum-andurine-detectableproteins,andshowingdifferentialexpressionofRNAindisease-damaged tissueswouldmakeidealdiagnosticproteinbiomarkersforthosediseases.Weshowedthatpredictedproteinbiomarkers aresignificantlyenrichedforknowndiagnosticproteinbiomarkersin22diseases,withenrichmentsignificantlyhigherin diseasesforwhichatleastthreedatasetsareavailable.Wethenusedthisstrategytosearchfornewbiomarkersindicating acuterejection(AR)acrossdifferenttypesoftransplantedsolidorgans.Weintegratedthreebiopsy-basedmicroarraystudies ofARfrompediatricrenal,adultrenalandadultcardiactransplantationandidentified45genesupregulatedinallthree. Fromthisset,wechose10proteinsforserumELISAassaysin39renaltransplantpatients,anddiscoveredthreethatwere significantly higher in AR. Interestingly, all three proteins were also significantly higher during AR in the 63 cardiac transplantrecipientsstudied.Our