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Modeling stochasticity and variability in gene regulatory networks

机译:在基因调控网络中模拟随机性和变异性

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Modeling stochasticity in gene regulatory networks is an important and complex problem in molecular systems biology. To elucidate intrinsic noise, several modeling strategies such as the Gillespie algorithm have been used successfully. This article contributes an approach as an alternative to these classical settings. Within the discrete paradigm, where genes, proteins, and other molecular components of gene regulatory networks are modeled as discrete variables and are assigned as logical rules describing their regulation through interactions with other components. Stochasticity is modeled at the biological function level under the assumption that even if the expression levels of the input nodes of an update rule guarantee activation or degradation there is a probability that the process will not occur due to stochastic effects. This approach allows a finer analysis of discrete models and provides a natural setup for cell population simulations to study cell-to-cell variability. We applied our methods to two of the most studied regulatory networks, the outcome of lambda phage infection of bacteria and the p53-mdm2 complex.
机译:基因调控网络中的随机性建模是分子系统生物学中一个重要且复杂的问题。为了阐明固有噪声,已成功使用了几种建模策略,例如Gillespie算法。本文提供了一种替代这些经典设置的方法。在离散范式中,基因调节网络的基因,蛋白质和其他分子成分被建模为离散变量,并被分配为逻辑规则,以描述它们通过与其他成分的相互作用进行调控。在以下假设下,在生物学功能级别上对随机性进行建模:即使更新规则的输入节点的表达级别保证激活或降解,也可能由于随机效应而不会发生该过程。这种方法可以对离散模型进行更精细的分析,并为细胞种群模拟提供自然的设置,以研究细胞之间的变异性。我们将我们的方法应用于两个研究最多的调节网络,即细菌的λ噬菌体感染的结果和p53-mdm2复合体。

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