Statistical Methods in Molecular Biology

Thisbookisintendedformolecularbiologistswhoperformquantitativeanalysesondata emanatingfromtheir?eldandforthestatisticianswhoworkwithmolecularbiologists andotherbiomedicalresearchers. Therearemanyexcellenttextbooksthatprovidefun- mentalcomponentsforstatisticaltrainingcurricula. Therearealsomany"byexpertsfor experts"booksinstatisticsandmolecularbiologywhichrequirein-depthknowledgein bothsubjectstobetakenfulladvantageof. Sofar,nobookinstatisticshasbeenpublished thatprovidesthebasicprinciplesofproperstatisticalanalysesandprogressestoamore advancedstatisticsinresponsetorapidlydevelopingtechnologiesandmethodologiesin the?eldofmolecularbiology. Respondingtothissituation,ourbookaimsatbridgingthegapbetweenthesetwo extremes. Molecularbiologistswillbene?tfromtheprogressivestyleofthebookwhere basicstatisticalmethodsareintroducedandgraduallyelevatedtoanintermediatelevel. Similarly,statisticianswillbene?tfromlearningthevariousbiologicaldatageneratedfrom the?eldofmolecularbiology,thetypesofquestionsofinteresttomolecularbiologists, andthestatisticalapproachestoanalyzingthedata. Thestatisticalconceptsandmethods relevanttostudiesinmolecularbiologyarepresentedinasimpleandpracticalmanner. Speci?cally,thebookcoversbasicandintermediatestatisticsthatareusefulforclassical and molecular biology settings and advanced statistical techniques that can be used to helpsolveproblemscommonlyencounteredinmodernmolecularbiologystudies,such assupervisedandunsupervisedlearning,hiddenMarkovmodels,manipulationandan- ysisofdatafromhigh-throughputmicroarrayandproteomicplatform,andsynthesisof these evidences.A tutorial-type format is used to maximize learning in some chapters. Advicefromjournaleditorsonpeer-reviewedpublicationandsomeusefulinformationon softwareimplementationarealsoprovided. Thisbookisrecommendedforuseassupplementarymaterialbothinsideandoutside classroomsorasaself-learningguideforstudents,scientists,andresearcherswhodealwith numericdatainmolecularbiologyandrelated?elds. Thosewhostartasbeginners,but desiretobeatanintermediatelevel,will?ndthisbookespeciallyusefulintheirlearning pathway. WewanttothankJohnWalker(serieseditor),PatrickMarton,DavidCasey,andAnne Meagher,(editorsatSpringerandHumana)andShanthyJaganathan(Integra-India). The followingpersonsprovidedusefuladviceandcommentsonselectionoftopics,referralto expertsineachtopic,and/orchapterreviewsthatwetrulyappreciate:StephenLooney(a former editor of this book), Stan Young, Dmitri Zaykin, Douglas Hawkins, Wei Pan, Alexandre Almeida, John Ho, Rebecca Doerge, Paula Trushin, Kevin Morgan, Jason Osborne,PeterWestfall,JennyXiang,Ya-linChiu,YolandaBarron,HuiboShao,Alvin Mushlin,andRonaldFanta. Drs. Bang,Zhou,andMazumdarwerepartiallysupported byClinicalTranslationalScienceCenter(CTSC)grant(UL1-RR024996).HeejungBang vii Contents Preface...vii Contributors...xi PARTIBASICSTATISTICS...1 1. ExperimentalStatisticsforBiologicalSciences...3 HeejungBangandMarieDavidian 2. NonparametricMethodsforMolecularBiology...105 KnutM. WittkowskiandTingtingSong 3. BasicsofBayesianMethods...155 SujitK. Ghosh 4. TheBayesiant-TestandBeyond ...179 MithatGonen PARTII DESIGNSANDMETHODSFORMOLECULARBIOLOGY...201 5. SampleSizeandPowerCalculationforMolecularBiologyStudies...203 Sin-HoJung 6. DesignsforLinkageAnalysisandAssociationStudiesofComplexDiseases...219 YuehuaCui,GengxinLi,ShaoyuLi,andRonglingWu 7. IntroductiontoEpigenomicsandEpigenome-WideAnalysis...243 MelissaJ. FazzariandJohnM. Greally 8. Exploration,Visualization,andPreprocessingofHigh-DimensionalData...267 ZhijinWuandZhiqiangWu PARTIII STATISTICALMETHODSFORMICROARRAYDATA ...285 9. IntroductiontotheStatisticalAnalysisofTwo-ColorMicroarrayData...287 MartinaBremer,EdwardHimelblau,andAndreasMadlung 10. BuildingNetworkswithMicroarrayData...315 BradleyM. Broom,WareeRinsurongkawong,LajosPusztai, andKim-AnhDo PARTIV ADVANCEDORSPECIALIZEDMETHODSFORMOLECULARBIOLOGY. . 345 11. SupportVectorMachinesforClassi?cation:AStatisticalPortrait...347 YoonkyungLee 12.AnOverviewofClusteringAppliedtoMolecularBiology ...369 RebeccaNugentandMarinaMeila ix xContents 13. HiddenMarkovModelandItsApplicationsinMotifFindings...405 JingWuandJunXie 14. DimensionReductionforHigh-DimensionalData...417 LexinLi 15. IntroductiontotheDevelopmentandValidationofPredictiveBiomarker ModelsfromHigh-ThroughputDataSets ...435 XutaoDengandFabienCampagne 16. Multi-geneExpression-basedStatisticalApproachestoPredicting Patients'ClinicalOutcomesandResponses...471 FengCheng,Sang-HoonCho,andJaeK. Lee 17. Two-StageTestingStrategiesforGenome-WideAssociationStudies inFamily-BasedDesigns ...485 AmyMurphy,ScottT. Weiss,andChristophLange 18. StatisticalMethodsforProteomics ...497 KlausJung PARTVMETA-ANALYSISFORHIGH-DIMENSIONALDATA ...509 19. StatisticalMethodsforIntegratingMultipleTypesofHigh-ThroughputData. . 511 YangXieandChulAhn 20. ABayesianHierarchicalModelforHigh-DimensionalMeta-analysis...531 FeiLiu 21. MethodsforCombiningMultipleGenome-WideLinkageStudies...541 TreciaA. KippolaandStephanieA. Santorico PARTVI OTHERPRACTICALINFORMATION ...561 22. ImprovedReportingofStatisticalDesignandAnalysis:Guidelines, Education,andEditorialPolicies...563 MadhuMazumdar,SampritBanerjee,andHeatherL. VanEpps 23. StataCompanion...599 JenniferSousaBrennan SubjectIndex...627 Contributors CHULAHN* Division of Biostatistics, Department of Clinical Sciences, The Harold C.