On the attenuation and amplification of molecular noise in genetic regulatory networks.
BACKGROUND
Noise has many important roles in cellular genetic regulatory functions at the nanomolar scale. At present, no good theory exists for identifying all possible mechanisms of genetic regulatory networks to attenuate the molecular noise to achieve regulatory ability or to amplify the molecular noise to randomize outcomes to the advantage of diversity. Therefore, the noise filtering of genetic regulatory network is an important topic for gene networks under intrinsic fluctuation and extrinsic noise.


RESULTS
Based on stochastic dynamic regulation equation, the intrinsic fluctuation in reaction rates is modeled as a state-dependent stochastic process, which will influence the stability of gene regulatory network, especially, with low concentrations of reacting species. Then the mechanisms of genetic regulatory network to attenuate or amplify extrinsic fluctuation are revealed from the nonlinear stochastic filtering point of view. Furthermore, a simple measure of attenuation level or amplification level of extrinsic noise for genetic regulatory networks is also introduced by nonlinear robust filtering method. Based on the global linearization scheme, a convenient method is introduced to measure noise attenuation or amplification for each gene of the nonlinear stochastic regulatory network by solving a set of filtering problems, which correspond to a set of linearized stochastic regulatory networks. Finally, by the proposed methods, several simulation examples of genetic regulatory networks are given to measure their robust stability under intrinsic fluctuations, and to estimate the genes' attenuation and amplification levels under extrinsic noises.


CONCLUSIONS
In this study, a stochastic nonlinear dynamic model is developed for genetic regulatory networks under intrinsic fluctuation and extrinsic noise. By the method we proposed, we could determine the robust stability under intrinsic fluctuations and identify the genes that are significantly affected by extrinsic noises, which we call the weak structure of the network. This method will be potential for robust gene circuit design in future, on which a drug design could be based.
Chen
Bor-Sen
BS
Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, 300, Taiwan. bschen@ee.nthu.edu.tw
Wang
Yu-Chao
YC
D000818:Animals; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013269:Stochastic Processes
D020543:Proteome