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调控相互作用网络的稳健性。一种具有不同层次(生理、代谢和遗传)应用的通用方法。

Robustness in regulatory interaction networks. A generic approach with applications at different levels: physiologic, metabolic and genetic.

机构信息

Université J. Fourier de Grenoble, TIMC-IMAG, CNRS UMR 5525, Faculté de Médecine, 38700 La Tronche, France.

Université de Lyon, École Normale Supérieure Lyon, LIP, CNRS UMR 5668, 69007 Lyon, France.

出版信息

Int J Mol Sci. 2009 Nov 20;10(10):4437-4473. doi: 10.3390/ijms10104437.

Abstract

Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control.

摘要

调控相互作用网络通常从其动力学方面进行研究(吸引子的存在,研究其稳定性)。我们还关注它们的鲁棒性,即它们提供相同时空模式的能力,以及抵抗外部干扰的能力,如网络相互作用结构中的节点或边的丢失、环境边界条件的变化,以及它们元素状态的更新计划(或更新模式)的变化(例如,如果这些元素是基因,它们的同步共表达模式与它们的顺序表达模式)。我们定义了调控网络基础相互作用图的边界、核心和关键顶点或边的一般概念,其消失会导致吸引子数量和性质的剧烈变化(例如,从双稳行为到单一周期状态的转变)或稳定域的范围发生变化。状态的动态转变将在阈值布尔自动机规则的框架内呈现。将给出不同层次的应用全景:脑和植物形态发生、延髓心肺调节、糖酵解/氧化代谢偶联,最终是细胞周期和羽毛形态发生的遗传控制。

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