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细胞调控的布尔网络模型:前景与局限

Boolean network models of cellular regulation: prospects and limitations.

作者信息

Bornholdt Stefan

机构信息

Institute for Theoretical Physics, University of Bremen, Bremen, Germany.

出版信息

J R Soc Interface. 2008 Aug 6;5 Suppl 1(Suppl 1):S85-94. doi: 10.1098/rsif.2008.0132.focus.

Abstract

Computer models are valuable tools towards an understanding of the cell's biochemical regulatory machinery. Possible levels of description of such models range from modelling the underlying biochemical details to top-down approaches, using tools from the theory of complex networks. The latter, coarse-grained approach is taken where regulatory circuits are classified in graph-theoretical terms, with the elements of the regulatory networks being reduced to simply nodes and links, in order to obtain architectural information about the network. Further, considering dynamics on networks at such an abstract level seems rather unlikely to match dynamical regulatory activity of biological cells. Therefore, it came as a surprise when recently examples of discrete dynamical network models based on very simplistic dynamical elements emerged which in fact do match sequences of regulatory patterns of their biological counterparts. Here I will review such discrete dynamical network models, or Boolean networks, of biological regulatory networks. Further, we will take a look at such models extended with stochastic noise, which allow studying the role of network topology in providing robustness against noise. In the end, we will discuss the interesting question of why at all such simple models can describe aspects of biology despite their simplicity. Finally, prospects of Boolean models in exploratory dynamical models for biological circuits and their mutants will be discussed.

摘要

计算机模型是有助于理解细胞生化调节机制的宝贵工具。此类模型的可能描述层次范围从对潜在生化细节的建模到自上而下的方法,后者使用复杂网络理论中的工具。在粗粒度方法中,调节回路以图论术语进行分类,调节网络的元素被简化为节点和链接,以便获得有关网络的架构信息。此外,在如此抽象的层面考虑网络动态似乎不太可能与生物细胞的动态调节活动相匹配。因此,当最近出现基于非常简单的动态元素的离散动态网络模型示例,而这些模型实际上确实与它们的生物学对应物的调节模式序列相匹配时,这着实令人惊讶。在此,我将回顾此类生物调节网络的离散动态网络模型,即布尔网络。此外,我们将研究扩展了随机噪声的此类模型,这些模型有助于研究网络拓扑结构在提供抗噪声鲁棒性方面的作用。最后,我们将讨论一个有趣的问题,即为何尽管这些模型很简单,但却能够描述生物学的某些方面。最后,还将讨论布尔模型在生物电路及其突变体的探索性动态模型中的前景。

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