Institut National de Recherche en Informatique et en Automatique, INRIA Grenoble - Rhône-Alpes, Montbonnot, France.
PLoS Comput Biol. 2010 Jun 10;6(6):e1000812. doi: 10.1371/journal.pcbi.1000812.
Gene regulatory networks consist of direct interactions but also include indirect interactions mediated by metabolites and signaling molecules. We describe how these indirect interactions can be derived from a model of the underlying biochemical reaction network, using weak time-scale assumptions in combination with sensitivity criteria from metabolic control analysis. We apply this approach to a model of the carbon assimilation network in Escherichia coli. Our results show that the derived gene regulatory network is densely connected, contrary to what is usually assumed. Moreover, the network is largely sign-determined, meaning that the signs of the indirect interactions are fixed by the flux directions of biochemical reactions, independently of specific parameter values and rate laws. An inversion of the fluxes following a change in growth conditions may affect the signs of the indirect interactions though. This leads to a feedback structure that is at the same time robust to changes in the kinetic properties of enzymes and that has the flexibility to accommodate radical changes in the environment.
基因调控网络包括直接相互作用，也包括通过代谢物和信号分子介导的间接相互作用。我们描述了如何使用生化反应网络的弱时间尺度假设和代谢控制分析的敏感性标准，从该模型中推导出这些间接相互作用。我们将此方法应用于大肠杆菌碳同化网络的模型。我们的结果表明，与通常假设的相反，所得到的基因调控网络是密集连接的。此外，该网络主要由符号决定，这意味着间接相互作用的符号由生化反应的通量方向确定，而与特定的参数值和速率定律无关。但是，通量的反转会影响间接相互作用的符号。这导致了一种反馈结构，它既能抵抗酶动力学特性的变化，又能适应环境的巨大变化。
