Non-Gaussian Distributions Affect Identification of Expression Patterns, Functional Annotation, and Prospective Classification in Human Cancer Genomes 英文参考文献.docVIP
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Non-Gaussian Distributions Affect Identification of Expression Patterns, Functional Annotation, and Prospective Classification in Human Cancer Genomes 英文参考文献
Non-GaussianDistributionsAffectIdentificationof
ExpressionPatterns,FunctionalAnnotation,and
ProspectiveClassificationinHumanCancerGenomes
NicholasF.Marko1*,RobertJ.Weil2
1CancerResearchUnitedKingdomCambridgeResearchInstituteandDepartmentofAppliedMathematicsandTheoreticalPhysics,CambridgeUniversity,Cambridge,
UnitedKingdom,2BrainTumorandNeuro-OncologyCenter,ClevelandClinic,Cleveland,Ohio,UnitedStatesofAmerica
Abstract
Introduction:Geneexpressiondataisoftenassumedtobenormally-distributed,butthisassumptionhasnotbeentested
rigorously. We investigate the distribution of expression data in human cancer genomes and study the implications of
deviationsfromthenormaldistributionfortranslationalmolecularoncologyresearch.
Methods:Weconductedacentralmomentsanalysisoffivecancergenomesandperformedempiricdistributionfittingto
examinethetruedistributionofexpressiondatabothonthecomplete-experimentandontheindividual-genelevels.We
usedavarietyofparametricandnonparametricmethodstotesttheeffectsofdeviationsfromnormalityongenecalling,
functionalannotation,andprospectivemolecularclassificationusingasixthcancergenome.
Results: Central moments analyses reveal statistically-significant deviations from normality in all of the analyzed cancer
genomes. We observe as much as 37% variability in gene calling, 39% variability in functional annotation, and 30%
variabilityinprospective,moleculartumorsubclassificationassociatedwiththiseffect.
Conclusions:Cancergeneexpressionprofilesarenotnormally-distributed,eitheronthecomplete-experimentoronthe
individual-gene level. Instead, they exhibit complex, heavy-tailed distributions characterized by statistically-significant
skewness and kurtosis. The non-Gaussian distribution of this data affects identification of differentially-expressed genes,
functional annotation, and prospective molecular classification. These effects may be reduced in some circumstances,
althoughnotcompletelyeliminated,byusingnonparametricanalytics.Thisanalysishighlightstwounreliablea
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