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Computational analysis of synergism in small networks with different logic
Journal of Biological Physics ( IF 1.8 ) Pub Date : 2022-12-29 , DOI: 10.1007/s10867-022-09620-0
Menghan Chen 1 , Ruiqi Wang 1
Affiliation  

Cell fate decision processes are regulated by networks which contain different molecules and interactions. Different network topologies may exhibit synergistic or antagonistic effects on cellular functions. Here, we analyze six most common small networks with regulatory logic AND or OR, trying to clarify the relationship between network topologies and synergism (or antagonism) related to cell fate decisions. We systematically examine the contribution of both network topologies and regulatory logic to the cell fate synergism by bifurcation and combinatorial perturbation analysis. Initially, under a single set of parameters, the synergism of three types of networks with AND and OR logic is compared. Furthermore, to consider whether these results depend on the choices of parameter values, statistics on the synergism of five hundred parameter sets is performed. It is shown that the results are not sensitive to parameter variations, indicating that the synergy or antagonism mainly depends on the network topologies rather than the choices of parameter values. The results indicate that the topology with “Dual Inhibition” shows good synergism, while the topology with “Dual Promotion” or “Hybrid” shows antagonism. The results presented here may help us to design synergistic networks based on network structure and regulation combinations, which has promising implications for cell fate decisions and drug combinations.



中文翻译:

不同逻辑小型网络协同作用的计算分析

细胞命运决定过程由包含不同分子和相互作用的网络调节。不同的网络拓扑可能对细胞功能表现出协同或拮抗作用。在这里,我们分析了六个最常见的具有调节逻辑 AND 或 OR 的小型网络,试图阐明与细胞命运决定相关的网络拓扑和协同(或拮抗)之间的关系。我们通过分叉和组合扰动分析系统地检查网络拓扑和调节逻辑对细胞命运协同作用的贡献。最初,在一组参数下,比较了三种具有 AND 和 OR 逻辑的网络的协同作用。此外,要考虑这些结果是否取决于参数值的选择,对五百个参数集的协同作用进行了统计。结果表明,结果对参数变化不敏感,表明协同或对抗主要取决于网络拓扑而不是参数值的选择。结果表明,具有“双重抑制”的拓扑显示出良好的协同作用,而具有“双重促进”或“混合”的拓扑显示出拮抗作用。这里展示的结果可能有助于我们设计基于网络结构和调控组合的协同网络,这对细胞命运决定和药物组合具有重要意义。结果表明,具有“双重抑制”的拓扑显示出良好的协同作用,而具有“双重促进”或“混合”的拓扑显示出拮抗作用。这里展示的结果可能有助于我们设计基于网络结构和调控组合的协同网络,这对细胞命运决定和药物组合具有重要意义。结果表明,具有“双重抑制”的拓扑显示出良好的协同作用,而具有“双重促进”或“混合”的拓扑显示出拮抗作用。这里展示的结果可能有助于我们设计基于网络结构和调控组合的协同网络,这对细胞命运决定和药物组合具有重要意义。

更新日期:2022-12-29
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