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Verification of multistability in gene regulation networks: A combinatorial approach

机译:基因调节网络中多合物的验证:一种组合方法

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Bi- or even multistable behavior is a recurrent phenomenon in gene regulation networks. These networks have the capacity to operate in two or more distinct modes in a stable manner. In this work, we consider gene regulation networks with known interaction structure but unknown reaction kinetics. Additionally, it is assumed that several distinct operation modes were observed experimentally whereby also the measurements of the individual protein concentrations are uncertain. For this setup, the important question of model validation is addressed: Can the given network structure in principle reproduce the observed operation modes? To approach this problem, the work builds on an existing modeling framework [4] which is appropriate to deal with uncertain gene regulation networks. By regarding each operation mode as a forward-invariant set in the state space and with the notion of compatible intervals, it is shown how the validation problem can be translated into a combinatorial one. An algorithm is developed which can efficiently solve the new problem. Finally, the well-known bistable lactose utilization network is analyzed with this new method.
机译:Bi-或甚至多个行为是基因调节网络中的复发现象。这些网络具有以稳定的方式以两个或更多个不同模式操作的容量。在这项工作中,我们考虑具有已知的相互作用结构但未知的反应动力学的基因调节网络。另外,假设实验观察到几种不同的操作模式,其中还要测量单个蛋白质浓度是不确定的。对于此设置,解决了模型验证的重要问题:给定的网络结构原则上是否再现观察到的操作模式?为了解决这个问题,工作建立在现有的建模框架[4]上,这适合处理不确定的基因调节网络。通过将每个操作模式视为状态空间中的前进不变集和兼容间隔的概念,示出了如何将验证问题转换为组合1。开发了一种算法,可以有效地解决新问题。最后,用这种新方法分析了众所周知的双稳态乳糖利用网络。

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