基于LHS方法NF-κB信号转导网络的多参数敏感性分析  

Multi-parameter Sensitivity Analysis of NF-κB Signaling Transduction Pathway using Latin Hypercube Sampling

作　　者：贾建芳[1,2] 岳红[2,3] 王宏[2] 

机构地区：[1]中北大学信息与通信工程学院,山西太原030051 [2]中国科学院自动化研究所,北京100080 [3]斯特莱斯克莱德大学电子与电气工程系,英国格拉斯哥G11QE

出　　处：《应用基础与工程科学学报》2008年第4期605-615,共11页Journal of Basic Science and Engineering

基　　金：国家自然科学基金资助(30770560)

摘　　要：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-κB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-κBn的影响程度.仿真结果表明,系统输出NF-κBn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-κBn的振荡特性,说明它们是NF-κB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.

关 键 词：NF-kB信号转导网络 多参数敏感性分析 Latin超立方抽样 系统生物学 

分 类 号：Q332[生物学—遗传学]