关键词: 细胞信号转导网络, 模型简化, 混合推理方法, 系统生物

Abstract: The mathematical model of cell signal transduction networks is highly nonlinear and complex, which involves a large number of variables and kinetics parameters. How to effectively develop the reduced-order model is a major problem for analyzing complex systems. In this work, a model reduction strategy via hybrid inference method is proposed for complex signal transducion networks. This approach synthesizes metabolic control analysis, sensitivity analysis, principal component analysis, and flux analysis to reduce the dimensions of the model and to decrease the number of the biological reactions. Using NF-κB signaling pathway as an example, the detailed model consists of 24 ordinary differential equations and 64 parameters. According to the model reduction strategy, the reduced-order model is composed of 17 ordinary differential equations, one algebraic equation, and 52 parameters. The simulation results demonstrate that the reduced-order model quantitatively predicts the dynamic characteristics of the system output, which are much the same as that of the detailed model. Therefore, the model reduction strategy provides guidance for the analysis and design of complex cell networks. It is more effective and more straightforward to estimate the unknown parameters by means of the reduced-order model.

Key words: cell signalling transduction networks, model reduction, hybrid inference method, systems biology