Computational Modeling in Biology, Institute for Bioinformatics and Systems Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
J Theor Biol. 2010 Oct 7;266(3):436-48. doi: 10.1016/j.jtbi.2010.07.007. Epub 2010 Jul 21.
We generalize random Boolean networks by softening the hard binary discretization into multiple discrete states. These multistate networks are generic models of gene regulatory networks, where each gene is known to assume a finite number of functionally different expression levels. We analytically determine the critical connectivity that separates the biologically unfavorable frozen and chaotic regimes. This connectivity is inversely proportional to a parameter which measures the heterogeneity of the update rules. Interestingly, the latter does not necessarily increase with the mean number of discrete states per node. Still, allowing for multiple states decreases the critical connectivity as compared to random Boolean networks, and thus leads to biologically unrealistic situations. Therefore, we study two approaches to increase the critical connectivity. First, we demonstrate that each network can be kept in its frozen regime by sufficiently biasing the update rules. Second, we restrict the randomly chosen update rules to a subclass of biologically more meaningful functions. These functions are characterized based on a thermodynamic model of gene regulation. We analytically show that their usage indeed increases the critical connectivity. From a general point of view, our thermodynamic considerations link discrete and continuous models of gene regulatory networks.
我们通过将硬二进制离散化软化为多个离散状态来推广随机布尔网络。这些多态网络是基因调控网络的通用模型,其中每个基因都被认为具有有限数量的功能不同的表达水平。我们通过分析确定了将生物不利的冻结和混沌状态分开的临界连接。该连接与度量更新规则异质性的参数成反比。有趣的是,后者不一定随每个节点的离散状态的平均数量而增加。尽管如此,与随机布尔网络相比,允许多个状态会降低临界连接,从而导致不切实际的生物学情况。因此,我们研究了两种提高临界连接的方法。首先,我们通过充分偏向更新规则来证明每个网络都可以保持在其冻结状态。其次,我们将随机选择的更新规则限制为生物学上更有意义的函数的子类。这些函数基于基因调控的热力学模型来表征。我们通过分析表明,它们的使用确实可以提高临界连接。从一般的角度来看,我们的热力学考虑将基因调控网络的离散和连续模型联系起来。