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

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

Conference Paper (2006)

Author(s)

TA Knijnenburg (TU Delft - Multimedia Computing)

Lodewyk F.A. Wessels (TU Delft - Multimedia Computing)

M.J.T. Reinders (TU Delft - Multimedia Computing)

Multimedia Computing

Techniek Conf.proc. > 3 pag Conference contrib. refereed Wiskunde en Informatica Technische Wiskunde en Informatica

To reference this document use:

https://resolver.tudelft.nl/uuid:e37433ef-dc09-4353-8ee9-aef227069893

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Publication Year

2006

Multimedia Computing

Bibliographical Note

Dit is opgenomen in Lecture Notes in Bioinformatics (4210) maar dat komt niet voor op de lijst en kan ook niet door mij worden toegevoegd@en

Pages (from-to)

271-284

ISBN (print)

3-540-46166-3

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.

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