通过布尔渠化实现分子网络控制
Molecular Network Control Through Boolean Canalization
AI总结：
本文研究布尔渠化在分子网络控制中的作用，提出基于布线图边识别控制目标和估计边删除后状态转换变化的方法，并在突变细胞周期和p53-mdm2模型上验证其有效性。
摘要：
布尔网络是分子相互作用网络的一类重要计算模型。布尔渠化是一种对布尔函数输入进行层次化聚类的方式，已在网络建模背景下得到广泛研究，其中每一层渠化都会为网络动力学增加一定程度的稳定性。近年来，动态网络控制方法已被用于设计新的治疗干预措施以及干细胞重编程等其他应用。本工作研究渠化在布尔分子网络控制中的作用。它提供了一种方法，用于识别网络布线图中需要控制的潜在边，以避免不希望的状态转换。该方法基于在不希望发生的转换上识别适当的输入-输出组合，这些组合可以利用网络布线图中的边进行修改。此外，还提出了一种方法，用于估计由于布线图中删除一条边而导致系统状态空间中发生变化的转换数量。本文将所提出的控制方法应用于一个突变细胞周期模型和一个 p53-mdm2 模型，以识别潜在的控制目标。
英文摘要：
Boolean networks are an important class of computational models for molecular interaction networks. Boolean canalization, a type of hierarchical clustering of the inputs of a Boolean function, has been extensively studied in the context of network modeling where each layer of canalization adds a degree of stability in the dynamics of the network. Recently, dynamic network control approaches have been used for the design of new therapeutic interventions and for other applications such as stem cell reprogramming. This work studies the role of canalization in the control of Boolean molecular networks. It provides a method for identifying the potential edges to control in the wiring diagram of a network for avoiding undesirable state transitions. The method is based on identifying appropriate input-output combinations on undesirable transitions that can be modified using the edges in the wiring diagram of the network. Moreover, a method for estimating the number of changed transitions in the state space of the system as a result of an edge deletion in the wiring diagram is presented. The control methods of this paper were applied to a mutated cell-cycle model and to a p53-mdm2 model to identify potential control targets.
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