细胞信号转导网络的复杂结构和动力学参数的不确定影响着系统的动态特性,如何定量确定参数变化对系统输出的影响,已经成为系统生物学研究的重要问题之一.以TNF-α诱导NF—kB信号转导网络为例,假定模型参数在其变化范围服从均匀分布,采用基于Latin超立方抽样的多参数敏感性分析方法,研究参数同时变化对系统输出NF—kBn的影响程度.仿真结果表明,系统输出NF—kBn对于参数k29、k28、k61、k36、k52,K31比较敏感,这些参数的变化显著影响着NF—kBn的振荡特性,说明它们是NF—kB信号转导网络的关键速率常数.
The dynamic behaviors of cells are deeply affected by structural complexity and parameters uncertainty of cell signaling transduction pathways. It is therefore necessary to study how the relationship between system behaviors and parameter variations can be quantitatively determined. Using a TNFα-induced NF-kB signaling transduction pathway model as an example, and assuming that parameters of the system model are independent of each other and obey the uniform distribution in the range of variations, multi-parameter sensitivity analysis of the output signal nuclear NF-kB with respect to the parameter variations is studied using Latin hypercube sampling method. The simulation results demonstrate that the output signal nuclear NF-kB is relatively sensitive to six key rate constants : k29, k28, k61, k36, ks2, and k31. As a result, the oscillation behavior of NF-kBn is significantly affected by these important parameters.