正负反馈耦合遗传电路中固有噪声诱导的状态跃迁

Pei Wang, Jinhu Lu, Yuhuan Zhang, M. Ogorzałek
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引用次数: 6

摘要

众所周知,基因调控回路可以通过确定性或随机方法来建模。本文首次用希尔动力学方法建立了三分量正负反馈耦合遗传回路的确定性模型。然后,利用Gellispie随机模拟方法研究了相应的随机模型。在对确定性系统进行分岔分析的基础上,进一步讨论了遗传电路的典型动力学行为,包括单稳定、双稳定、可激性和振荡。本文旨在进一步研究随机模型中固有噪声对稳态转换的影响。它包括:i)对于确定性双稳态区域内的参数,在系统体积不太大的情况下,本然噪声可能诱发双稳态切换,这可以通过产生新的稳定稳态来观察;ii)对于确定性可激发区的参数,在系统体积非常大的情况下,固有噪声会引起周期切换,这种切换可以通过另一个不稳定稳态的稳定化和两个稳定状态之间的切换来观察;iii)当这两个模型中引入时滞时,可以观察到类似的现象。上述结果必将加深对遗传电路不同模型之间内在关系的认识。它对现实世界的工程应用,如合成电路的工程设计有一定的启示。
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Intrinsic noise induced state transition in coupled positive and negative feedback genetic circuit
It is well known that gene regulatory circuits can be modeled by the deterministic or stochastic approach. In this paper, a three-component coupled positive and negative feedback genetic circuit is firstly modeled deterministically by Hill kinetics. Then, a corresponding stochastic model is also investigated by using Gellispie's stochastic simulation. Some typical dynamical behaviors of the genetic circuit are further discussed based on the bifurcation analysis of deterministic system, including monostability, bistability, excitability, and oscillation. This paper aims to further investigate the effect of intrinsic noise inherently in stochastic models on steady states transition. It includes: i) For the parameters in deterministically bistable region, intrinsic noise may induce bistable switch for the not too large system volume, which can be observed by the generation of a new stable steady state; ii) For the parameters in deterministically excitable region, intrinsic noise may induce periodic switch for the very large system volume, which can be observed by the stabilization of another unstable steady state and the switching between two stable states; iii) When time delays are introduced in these two models, similar phenomena can be observed. The above results will certainly increase the understanding of the inner relationships between different modeling for the genetic circuit. It sheds some light on the real- world engineering applications, such as the engineering design of synthetic circuits.
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