Effect of Size and Heterogeneity of Samples on Biomarker Discovery Synthetic and Real Data Assessment 英文参考文献.docVIP

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Effect of Size and Heterogeneity of Samples on Biomarker Discovery Synthetic and Real Data Assessment 英文参考文献.doc

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Effect of Size and Heterogeneity of Samples on Biomarker Discovery Synthetic and Real Data Assessment 英文参考文献

EffectofSizeandHeterogeneityofSampleson BiomarkerDiscovery:SyntheticandRealData Assessment BarbaraDiCamillo1,TizianaSanavia1,MatteoMartini1,GiuseppeJurman2,FrancescoSambo1 ,Annalisa Barla3,MargheritaSquillario3,CesareFurlanello2,GiannaToffolo1,ClaudioCobelli1* 1InformationEngineeringDepartment,UniversityofPadova,Padova,Italy,2FondazioneBrunoKessler,Povo,Trento,Italy,3DepartmentofComputerandInformation Science,UniversityofGenova,Genova,Italy Abstract Motivation:Theidentificationofrobustlistsofmolecularbiomarkersrelatedtoadiseaseisafundamentalstepforearly diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide resultswithlimitedoverlap.Thesedifferencesareimputableto1)datasetsize(fewsubjectswithrespecttothenumberof features); 2) heterogeneity of the disease; 3) heterogeneity of experimental protocols and computational pipelines employedintheanalysis.Inthispaper,wefocusonthefirsttwoissuesandassess,bothonsimulated(throughaninsilico regulation network model) and real clinical datasets, the consistency of candidate biomarkers provided by a number of differentmethods. Methods: We extensively simulated the effect of heterogeneity characteristic of complex diseases on different sets of microarraydata.Heterogeneitywasreproducedbysimulatingbothintrinsicvariabilityofthepopulationandthealteration ofregulatorymechanisms.Populationvariabilitywassimulatedbymodelingevolutionofapoolofsubjects;then,asubset ofthemunderwentalterationsinregulatorymechanismssoastomimicthediseasestate. Results:Thesimulateddataallowedustooutlineadvantagesanddrawbacksofdifferentmethodsacrossmultiplestudies and varying number of samples and to evaluate precision of feature selection on a benchmark with known biomarkers. Althoughcomparableclassificationaccuracywasreachedbydifferentmethods,theuseofexternalcross-validationloopsis helpfulinfindingfeatureswithahigherdegreeofprecisionandstability.Applicationtorealdataconfirmedtheseresults. Citation:DiCamill