具有协同调节规则的基因调控网络的稳定性和结构性质
Stability and Structural Properties of Gene Regulation Networks with Coregulation Rules
摘要：
在细菌和真核生物系统中，基因组表达的共调节已经被广泛地经验性地证明。这种共调节可以通过使用共享的调节基序来产生，其允许跨基因组的功能相关基因的模块（和模块组）的协调表达。协同调节也可以通过多基因复合体通过染色体成环的物理关联产生，然后一起转录。我们提出了一个一般的形式主义的随机布尔网络（RBN）的框架内的协同调节规则建模，并开发特定的模型与模块化结构的转录因子网络（包括模块组，和多输入模块（MIM）与自动调节）和多基因复合体（包括多基因复合体成员之间的层次分化）。我们开发了一个平均场的方法来分析大型网络的稳定性，将协同调节，并表明自动调节MIM和层次基因复合体模型可以实现更大的稳定性比网络没有协同调节的规则匹配激活频率。我们通过仿真进一步分析了这两种小网络的稳定性。我们还描述了几个一般性质的瞬态和吸引子的层次协同调节模型，并显示使用模拟的稳态分布分解层次作为贝叶斯网络的马尔可夫跳跃过程模拟的RBN模型。
英文摘要：
Coregulation of the expression of groups of genes has been extensively demonstrated empirically in bacterial and eukaryotic systems. Such coregulation can arise through the use of shared regulatory motifs, which allow the coordinated expression of modules (and module groups) of functionally related genes across the genome. Coregulation can also arise through the physical association of multi-gene complexes through chromosomal looping, which are then transcribed together. We present a general formalism for modeling coregulation rules in the framework of Random Boolean Networks (RBN), and develop specific models for transcription factor networks with modular structure (including module groups, and multi-input modules (MIM) with autoregulation) and multi-gene complexes (including hierarchical differentiation between multi-gene complex members). We develop a mean-field approach to analyse the stability of large networks incorporating coregulation, and show that autoregulated MIM and hierarchical gene-complex models can achieve greater stability than networks without coregulation whose rules have matching activation frequency. We provide further analysis of the stability of small networks of both kinds through simulations. We also characterize several general properties of the transients and attractors in the hierarchical coregulation model, and show using simulations that the steady-state distribution factorizes hierarchically as a Bayesian network in a Markov Jump Process analogue of the RBN model.
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