Adjusting Phenotypes by Noise Control 英文参考文献.docVIP

AdjustingPhenotypesbyNoiseControl KyungH.Kim*,HerbertM.Sauro DepartmentofBioengineering,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica Abstract Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineeringperspective,therehavebeeneffortsfocusedontheoryandexperimentstocontrolnoiselevelsbyperturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly dueto the intractablemathematicalstructureofnoisepropagationthroughreactionnetworks.Here,weprovideanumericalanalysis methodbyquantifyingtheparametricsensitivityofnoisecharacteristicsatthelevelofthelinearnoiseapproximation.Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonallycontrolthemeanandnoiselevelsandcancontrolsystemdynamicssuchasnoisyoscillations.Asanillustration weappliedourmethodtoHIVandyeastgeneexpressionsystemsandmetabolicnetworks.Theoscillatorysignalcontrol wasappliedtop53oscillationsfromDNAdamage.Furthermore,weshowedthattheefficiencyoforthogonalcontrolcanbe enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belongingtocontinuoustimeMarkoviansystemssuchasbiologicalandchemicalreactionsystems,andevencomputerand social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks. Citation:KimKH,SauroHM(2012)AdjustingPhenotypesbyNoiseControl.PLoSComputBiol8(1):e1002344.doi:10.1371/journal.pcbi.1002344 Editor:FeilimMacGabhann,JohnsHopkinsUniversity,UnitedStatesofAmerica ReceivedJuly7,2011;AcceptedNovember23,2011;PublishedJanuary12,2012 Copyright: ? 2012 Kim, Sauro. This is an open-access article distributed under the terms of the Creative Commons Attribution Lic