Condition transition analysis reveals TF activity to nutrient-limitation-specific effects of oxygen presence in yeast

TA Knijnenburg, LFA Wessels, MJT Reinders

Research output: Chapter in Book/Conference proceedings/Edited volumeConference contributionScientificpeer-review

Abstract

Regulatorynetworksareusuallypresentedasgraphstructuresshowingthe(combinatorial)regulatorye¿ectoftranscriptionfactors(TF¿s)onmodulesofsimilarlyexpressedorotherwiserelatedgenes.However,fromthesenetworksitisnotclearwhenandhowTF¿sareactivated.TheactualconditionsorperturbationsthattriggerachangeintheactivityofTF¿sshouldbeacrucialpartofthegeneratedregulatorynetwork. Here,wedemonstratethepowertouncoverTFactivitybyfocusingonasmall,homogeneous,yetwellde¿nedsetofchemostatcultivationexperiments,wherethetranscriptionalresponseofyeastgrownunderfourdi¿erentnutrientlimitations,bothaerobicallyaswellasanaerobicallywasmeasured.Wede¿neaconditiontransitionasaninstantchangeinyeast¿sextracellularenvironmentbycomparingtwocultivationconditions,whereeitherthelimitednutrientortheoxygenavailabilityisdi¿erent.Di¿erentialgeneexpressionasaconsequenceofsuchaconditiontransitionisrepresentedinatertiarymatrix,wherezeroindicatesnochangeinexpression;1and-1respectivelyindicateanincreaseanddecreaseinexpressionasaconsequenceofaconditiontransition.WeuncoverTFactivitybyassessingsigni¿cantTFbindinginthepromotorregionofgenesthatbehaveaccordinglyataconditiontransition.Theinterrelatednessoftheconditionsinthecombinatorialsetupisexploitedbyperformingspeci¿chypergeometricteststhatallowforthediscoveryofbothindividualandcombinede¿ectsofthecultivationparametersonTFactivity.Additionally,wecreateaweight-matrixindicatingtheinvolvementofeachTFineachoftheconditiontransitionsbyposingourproblemasanorthogonalProcrustesproblem.WeshowthattheProcrustesanalysisstrengthensandbroadenstheuncoveredrelationships. Theresultingregulatorynetworkrevealsnutrient-limitation-speci¿ce¿ectsofoxygenpresenceonexpressionbehaviorandTFactivity.Ouranalysisidenti¿esmanyTF¿sthatseemtoplayaveryspeci¿cregulatoryroleatthenutrientandoxygenavailabilitytransitions.
Original languageUndefined/Unknown
Title of host publicationComputational Methods in Systems Biology
EditorsC Priami
Place of PublicationBerlin,Heidelberg
PublisherSpringer
Pages271-284
Number of pages14
ISBN (Print)3-540-46166-3
Publication statusPublished - 2006
EventInternational Conference Computational Methods in Systems Biology, Trento, Italy - Berlin,Heidelberg
Duration: 18 Oct 200619 Oct 2006

Publication series

Name
PublisherSpringer
Name
Volume4210

Conference

ConferenceInternational Conference Computational Methods in Systems Biology, Trento, Italy
Period18/10/0619/10/06

Keywords

  • Wiskunde en Informatica
  • Techniek
  • technische Wiskunde en Informatica
  • conference contrib. refereed
  • Conf.proc. > 3 pag

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