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Stochastic models for regulatory networks of the genetic toggle switch

机译:遗传拨动开关调控网络的随机模型

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摘要

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.
机译:从细菌中的λ噬菌体转换到哺乳动物细胞中的细胞信号转导途径,双稳性在广泛的生物系统中产生。调节机制的变化可能导致双稳态系统中的遗传转换。最近,越来越多的以双峰态分布的形式出现的实验证据表明,噪声在双稳态系统的转换中起着非常重要的作用。尽管确定性模型已用于研究各种系统条件下双稳态特性的存在,但这些模型无法实现遗传转换中的细胞间波动。但是,由于缺乏对生化反应,动力学速率和分子数的详细了解,用于研究双稳态系统中噪声影响的随机模型的开发存在滞后性。在这项工作中,我们通过将Poisson随机变量引入到由常微分方程描述的确定性模型中,开发了一种以前未描述的通用技术,用于为大规模遗传调控网络开发定量随机模型。已经提出了与SOS信号通路或群体感应信号通路接口的遗传拨动开关的两个随机模型,并且我们已经成功地实现了显示双峰种群分布的实验结果。由于引入的随机模型基于广泛使用的常微分方程模型,因此这项工作的成功表明,这种方法对于研究大规模遗传调控网络中的噪声非常有前途。

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