Systems Biology and Mathematical Modeling Group, Max-Planck Institute of Molecular Plant Physiology, 14476 Potsdam, Germany.
J Theor Biol. 2012 Dec 7;314:192-203. doi: 10.1016/j.jtbi.2012.08.018. Epub 2012 Aug 23.
Understanding the emerging properties of complex biological systems is in the crux of systems biology studies. Computational methods for elucidating the role of each component in the synergetic interplay can be used to identify targets for genetic and metabolic engineering. In particular, we aim at determining the importance of reactions in a metabolic network with respect to a specific biological function. Therefore, we propose a novel game-theoretic framework which integrates restricted cooperative games with the outcome of flux balance analysis. We define productivity games on metabolic networks and present an analysis of their unrestricted and restricted variants based on the game-theoretic solution concept of the Shapley value. Correspondingly, this concept provides a characterization of the robustness and functional centrality for each enzyme involved in a given metabolic network. Furthermore, the comparison of two different environments - feast and famine - demonstrates the dependence of the results on the imposed flux capacities.
理解复杂生物系统的新兴特性是系统生物学研究的核心。阐明协同作用中每个组件作用的计算方法可用于确定遗传和代谢工程的目标。特别是，我们旨在确定代谢网络中反应对于特定生物功能的重要性。因此，我们提出了一种新的博弈论框架，将受限合作博弈与通量平衡分析的结果相结合。我们定义了代谢网络上的生产力博弈，并基于 Shapley 值的博弈论解决方案概念分析了它们的无约束和受限变体。相应地，该概念为给定代谢网络中涉及的每个酶的鲁棒性和功能中心性提供了特征描述。此外，对两种不同环境（盛宴和饥荒）的比较表明，结果取决于施加的通量容量。
