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基于基因调控网络中 canalizing 能力稳定性的约简的网络分类——布尔网络建模视角。

Network Classification Based on Reducibility With Respect to the Stability of Canalizing Power of Genes in a Gene Regulatory Network - A Boolean Network Modeling Perspective.

出版信息

IEEE/ACM Trans Comput Biol Bioinform. 2022 Jan-Feb;19(1):558-568. doi: 10.1109/TCBB.2020.3005313. Epub 2022 Feb 3.

DOI:10.1109/TCBB.2020.3005313
PMID:32750876
Abstract

A key objective of studying biological systems is to design therapeutic intervention strategies for beneficially altering cell dynamics. Derivation of control policies is hindered by the high-dimensional state spaces associated with gene regulatory networks. Hence, it is critical to reduce the network complexity and the paper aims to address this issue by focusing on the distribution of the canalizing power (CP) of the genes in the model. Canalizing genes enforce broad corrective actions on cellular processes and play a crucial role in producing optimal reactions to external stimuli. Therefore, it is critical to reduce the network while preserving the canalizing power of genes. We reduce Boolean networks with perturbation by removing genes with the smallest canalizing power consecutively, and evaluate the stability of canalizing power. A systematic empirical study demonstrates that there are two classes of networks, reducible and irreducible with respect to the preservation of canalizing power of the genes. Based on these observations, we introduce the definition of reducible networks and proceed with the problem of selecting the relevant network features that allow for discriminating networks from the two different classes. We demonstrate the efficacy of the selected features on synthetic and real gene regulatory networks.

摘要

研究生物系统的一个关键目标是设计治疗干预策略,以有益地改变细胞动力学。由于与基因调控网络相关的高维状态空间,控制策略的推导受到阻碍。因此,降低网络复杂性至关重要,本文旨在通过关注模型中基因的 canalizing 能力 (CP) 的分布来解决这个问题。Canalizing 基因对细胞过程施加广泛的纠正作用,在对外界刺激产生最佳反应方面起着至关重要的作用。因此,在降低网络的同时保持基因的 canalizing 能力至关重要。我们通过连续去除具有最小 canalizing 能力的基因来减少受干扰的布尔网络,并评估 canalizing 能力的稳定性。系统的经验研究表明,存在两类网络,即可约和不可约,与基因 canalizing 能力的保持有关。基于这些观察,我们引入了可约网络的定义,并着手解决选择相关网络特征的问题,这些特征允许从两个不同的类别中区分网络。我们在合成和真实基因调控网络上证明了所选特征的有效性。

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