Bioinformatics for Systems Biology

With the completion of the human genome project, followed by the rise in high-throughput technologies like the various microarray and now high throughput genomic sequencing platforms,weexperiencedthebirthofSystemsBiologyafteritslonggestation. Thisrevolutionis markedbyachangeintheresearchparadigmfromthesinglesmall-scaleexperiment,i. e. ,following thechangeofacomponentinamulticomponentsystem,toonethatattemptstosimultaneously monitorthechangeoftensofthousandsofmoleculeswithinthisbody. Thisclearlynecessitatesthe unparalleleduseofproject-specificinformatictools,which,todate,requiresanunprecedentedlevel ofdevelopmenttocollect,manageandminethedataforinterestingassociations. Tobegintounderstandthisinformationwenowrelyonstatisticalanalysistoaidinourselection ofthefruitfromthetree. However,thisoftentakesusonajourneyintoanewfieldforwhichweare notyetprepared. SamuelJohnson(1709-1784)foreshadowedthedilemmawewouldfaceand characterizeditasfollows:"Knowledgeisoftwokinds. Weknowasubjectourselves,orweknow wherewecanfindinformationonit. "Itisforthelatterthatweroutinelyturntotheliterature. The rateofgrowthoftheliteratureparallelsthatofsequencingdataandthearraydataplacingan almostimpossibletaskbeforeeachinvestigator. Topartiallyeasethisburdenweareagainturning towardsdevelopinginformaticaidsthatminetheliteratureanddatatodevelopsummariesand associationstodirectlyaddressthequestionsposedandthenewhypothesesthataretobetested. Althoughmoreclearlyarticulated,weagainfacesimilarchallengesasthosetackledduringthe courseofthehumangenomeproject. Itisessentialthatthetrainingofthebiologistandcomput- scientistoccurinaninterdisciplinaryenvironmentofcross-fertilization. Withthisgoalinmindthe textbook"BioinformaticsforSystemsBiology"wasundertaken. 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 Structu...