Messina A Novel Analysis Tool to Identify Biologically Relevant Molecules in Disease 英文参考文献.docVIP

Messina A Novel Analysis Tool to Identify Biologically Relevant Molecules in Disease 英文参考文献.doc

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Messina A Novel Analysis Tool to Identify Biologically Relevant Molecules in Disease 英文参考文献

Messina:ANovelAnalysisTooltoIdentifyBiologically RelevantMoleculesinDisease MarkPinese1*,ChristopherJ.Scarlett1,JamesG.Kench1,2,3,EmilyK.Colvin1,DavendraSegara1,4, SusanM.Henshall1,RobertL.Sutherland1,AndrewV.Biankin1,4 1CancerResearchProgram,GarvanInstituteofMedicalResearch,Darlinghurst,NewSouthWales,Australia,2CentralClinicalSchool,UniversityofSydney,Camperdown, New South Wales, Australia, 3Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia, 4Division of Surgery, BankstownHospital,Bankstown,NewSouthWales,Australia Abstract Background: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantiallydifferentclinicalcourses.Thisdiversityhasbecomethebasisforthedefinitionofmolecularphenotypes,with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrationswhichdefinebiologicallyrelevantsubtypes. Methodology/PrincipalFindings:HerewepresentMessina,amethodthatcanidentifythosegenesthatonlysometimes showaberrantexpressionincancer.WedemonstratewithsimulateddatathatMessinaishighlysensitiveandspecificwhen used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporaryanalysistechniques.WeillustrateMessinabyusingittodetecttheaberrantexpressionofagenethatmay playanimportantroleinpancreaticcancer. Conclusions/Significance:Messinaallowsthedetectionofgeneswithprofilestypicalofmarkersofmolecularsubtype,and complementsexistingmethodstoassisttheidentificationofsuchmarkers.Messinaisapplicabletoanyglobalexpression profilingdata,andtoallowitseasyapplicationhasbeenpackagedintoafreely-availablestand-alonesoftwarepackage. Citation: Pinese M, Scarlett CJ, Kench JG, Colvin EK, Segara D, et al. (2009) Messina: A Novel Analysis Tool to Identif

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