TY - GEN
T1 - Condition transition analysis reveals TF activity to nutrient-limitation-specific effects of oxygen presence in yeast
AU - Knijnenburg, TA
AU - Wessels, LFA
AU - Reinders, MJT
N1 - 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
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Wiskunde en Informatica
KW - Techniek
KW - technische Wiskunde en Informatica
KW - conference contrib. refereed
KW - Conf.proc. > 3 pag
UR - http://www.springerlink.com/content/01342gt6h02k533h/fulltext.pdf
M3 - Conference contribution
SN - 3-540-46166-3
SP - 271
EP - 284
BT - Computational Methods in Systems Biology
A2 - Priami, C
PB - Springer
CY - Berlin,Heidelberg
T2 - International Conference Computational Methods in Systems Biology, Trento, Italy
Y2 - 18 October 2006 through 19 October 2006
ER -