Conradi Carsten, Flockerzi Dietrich, Raisch Jörg, Stelling Jörg
Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany.
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19175-80. doi: 10.1073/pnas.0705731104. Epub 2007 Nov 27.
In analyzing and mathematical modeling of complex (bio)chemical reaction networks, formal methods that connect network structure and dynamic behavior are needed because often, quantitative knowledge of the networks is very limited. This applies to many important processes in cell biology. Chemical reaction network theory allows for the classification of the potential network behavior-for instance, with respect to the existence of multiple steady states-but is computationally limited to small systems. Here, we show that by analyzing subnetworks termed elementary flux modes, the applicability of the theory can be extended to more complex networks. For an example network inspired by cell cycle control in budding yeast, the approach allows for model discrimination, identification of key mechanisms for multistationarity, and robustness analysis. The presented methods will be helpful in modeling and analyzing other complex reaction networks.
在复杂(生物)化学反应网络的分析和数学建模中,需要将网络结构与动态行为联系起来的形式化方法,因为通常情况下,网络的定量知识非常有限。这适用于细胞生物学中的许多重要过程。化学反应网络理论允许对潜在的网络行为进行分类——例如,关于多个稳态的存在——但在计算上仅限于小型系统。在这里,我们表明,通过分析称为基本通量模式的子网络,该理论的适用性可以扩展到更复杂的网络。对于一个受芽殖酵母细胞周期控制启发的示例网络,该方法允许进行模型判别、确定多稳态的关键机制以及进行鲁棒性分析。所提出的方法将有助于对其他复杂反应网络进行建模和分析。