WebeginthisexplorationwithPartI,toprovidethecomputerscientistwithanintroductiontothe underlyingprinciplesofcellbiology. ThisisfollowedbyabriefintroductioninPartIIasameansfor thebiologisttobecomefamiliarwithconceptsandthestatisticalanalysisoflargedatasets. PartIII thendescribes,todate,thebestcharacterizeduseofthemicroarrayplatformthatisnowmoving towardswholegenomeanalysis. Withallofthisdata,howdowebeginanalysisforcommonelements guidingtheunderlyingprinciples?ThisisdiscussedinPartIVwhichleadstoPartVandPartVIto test,insilico,therelationshipsonawidescaleinordertoassesstheirapplicability. Upondeveloping theassociations,PartVIIaskshowdoesthisinformationrelatetowhatwasmeasured?Asthesebasic principlesaredevelopedfroman‘‘omics’’drivenbiologicalsystemsapproach,theyareappliedin PartVIIItotranslationalmedicine. Anexcellentexampleisthenewterm‘‘personalizedmedicine’’ thatisbeginningtoreverberateinclinicalcare. ItistheculminationoftheSystemsBiologyrevolution wheretechnologicaladvancesandcross-fertilizationhavedriventhefieldtomaturetothepoint whereitisbeingincorporatedinatruebench-to-bedsidemanner. Asyoureadthechapters,youwillfindthattheycanstandalone,yetcanbecombinedto emphasizetheintegralroleofinformaticsinSystemsBiology. Mostofthefiguresandtablesarein greyscale. IwouldencourageyoutoviewthosethatbenefitfromcolorontheaccompanyingCD. ThematerialcontainedontheCDprovidesanexcellentsourceofslidesforyourlecturesand presentations. v vi Preface Thechapter-relatedGlossaryandAbbreviationssectionwillassistinfamiliarizingyouwiththe terms. Youwillalsofindtheliteratureandsuggestedreadingsections,includingkeyreferences, veryusefulasyoudelveintothesubjectmatter. Technology,byitsverymeaningimpliesrefinement and change. The informatics approaches used in systems biology are continually subject to refinement. Withthisreality,youareencouragedtoutilizethewebsiteinformationprovidedin variouschapterstohelpaccessthemostcurrentinformationandresourcesavailable. AsSystems Biologydevelopsweareabletowitnessgrowingpainsandmilestones. Withcontinuedinformatic andbiologicalcross-fertilization,advancementsinSystemsBiologywillrevolutionizepersonalized medicineansweringquestionsbyintegratinginformationinunexpectedways. Contents PartI LifeofaCellandItsAnalysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 StructureandFunctionoftheNucleusandCellOrganelles. . . . . . . . . . . . . . . . . . . . . . . . 3 JonHolyandEdPerkins 2 TranscriptionandtheControlofGeneExpression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 NadineWiper-BergeronandIlonaS. Skerjanc 3 RNAProcessingandTranslation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 ChristinaKaramboulas,NadineWiper-Bergeron,andIlonaS. Skerjanc 4 DNAReplication,Recombination,andRepair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 LindaB. Bloom 5 CellSignaling. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 DanielA. RappoleeandD. RandallArmant 6 EpigeneticsofSpermiogenesis–CombiningInSilicoandProteomicApproaches intheMouseModel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 SophieRousseauxandMyriamFerro 7 GenomicToolsforAnalyzingTranscriptionalRegulatoryNetworks. . . . . . . . . . . . . . . . . 119 JohnJ. Wyrick PartII StatisticalToolsandTheirApplication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 8 ProbabilityandHypothesisTesting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 MichaelL. Kruger 9 StochasticModelsforBiologicalPatterns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 GautamB. Singh 10 PopulationGenetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 JillS. Barnholtz-SloanandHemantK. Tiwari 11 Statistica