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 appr