IEEE Trans Biomed Circuits Syst. 2008 Jun;2(2):114-32. doi: 10.1109/TBCAS.2008.926728.
Biochemical regulatory networks including genes, proteins and other regulatory molecules suffer from internal parametrical fluctuations (thermal, transcriptional, and splicing) as well as external noises (environmental and intercellular). Robustness is an essential property of intracellular biochemical regulatory networks to attenuate the effects of internal fluctuation and external noise. In this study, several system control schemes are proposed for the robust circuit control design of stochastic linear and nonlinear biochemical regulatory networks. First, the robust stability of genetic and proteomic regulatory networks is discussed under internal fluctuations. Then, the filtering ability of external noises is analyzed for stochastic biochemical regulatory networks. For the case where a biochemical regulatory network is not sufficiently robust to tolerate internal fluctuation and does not have enough filtering ability to filter the external noise, how to improve the robustness and noise filtering ability of stochastic biochemical regulatory networks by engineered control mechanisms is also proposed via biochemical circuit design. The proposed robust gene circuit design principles have potential applications for robust biosynthetic network design. Finally, two design examples are given in-silico to illustrate the design procedure and to confirm the performance of the proposed robust circuit design method.
生化调节网络包括基因、蛋白质和其他调节分子，它们会受到内部参数波动（热、转录和剪接）以及外部噪声（环境和细胞间）的影响。鲁棒性是细胞内生化调节网络的一个重要特性，可减弱内部波动和外部噪声的影响。本研究针对随机线性和非线性生化调节网络的鲁棒电路控制设计，提出了几种系统控制方案。首先，在内部波动下讨论了遗传和蛋白质组调节网络的鲁棒稳定性。然后，分析了随机生化调节网络对外界噪声的滤波能力。对于生化调节网络不够鲁棒以耐受内部波动，并且没有足够的滤波能力来过滤外部噪声的情况，还通过生化电路设计提出了如何通过工程控制机制来提高随机生化调节网络的鲁棒性和噪声滤波能力。所提出的鲁棒基因电路设计原则对于稳健生物合成网络设计具有潜在的应用价值。最后，通过计算机仿真给出了两个设计实例，以说明设计过程并验证所提出的鲁棒电路设计方法的性能。
