Single Sample Expression-Anchored Mechanisms Predict Survival in Head and Neck Cancer 英文参考文献.docVIP

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Single Sample Expression-Anchored Mechanisms Predict Survival in Head and Neck Cancer 英文参考文献.doc

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Single Sample Expression-Anchored Mechanisms Predict Survival in Head and Neck Cancer 英文参考文献

SingleSampleExpression-AnchoredMechanismsPredict SurvivalinHeadandNeckCancer XinanYang1,2,KellyRegan1¤,YongHuang1,2,QingbeiZhang1,2,JianrongLi1,2¤,TanguyY.Seiwert3,4 EzraE.W.Cohen3,4,H.RosieXing4,5,6,YvesA.Lussier1,2,4,5,6,7¤ , * 1Center for Biomedical Informatics, The University of Chicago, Chicago, Illinois, United States of America, 2Section of Genetic Medicine, The University of Chicago, Chicago,Illinois,UnitedStatesofAmerica,3SectionofHematology/OncologyoftheDepartmentofMedicine,TheUniversityofChicago,Chicago,Illinois,UnitedStatesof America,4ComprehensiveCancerCenter,TheUniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica,5DepartmentsofPathologyandofCellularandRadiation Oncology,The University ofChicago, Chicago,Illinois, United States ofAmerica, 6LudwigCenterforMetastasis Research, The University ofChicago, Chicago,Illinois, United States of America, 7Computation Institute, Institute for Translational Medicine, and Institute for Genomics and Systems Biology, The University of Chicago, Chicago,Illinois,UnitedStatesofAmerica Abstract Geneexpressionsignaturesthatarepredictiveoftherapeuticresponseorprognosisareincreasinglyusefulinclinicalcare; however,mechanistic(andintuitive)interpretationofexpressionarraysremainsanunmetchallenge.Additionally,thereis surprisinglylittlegeneoverlapamongdistinctclinicallyvalidatedexpressionsignatures.These‘‘causalitychallenges’’hinder theadoptionofsignaturesascomparedtofunctionallywell-characterizedsinglegenebiomarkers.Toincreasetheutilityof multi-genesignaturesinsurvivalstudies,wedevelopedanovelapproachtogenerate‘‘personalmechanismsignatures’’of molecular pathways and functions from gene expression arrays. FAIME, the Functional Analysis of Individual Microarray Expression,computesmechanismscoresusingrank-weightedgeneexpressionofanindividualsample.Bycomparinghead andnecksquamouscellcarcinoma(HNSCC)sampleswithnon-tumorcontroltissues,theprecisionandrecallofderegulated FAIME-derived mechanisms of pathways and molecular functio