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具有延迟的基因反馈回路中发生振荡的可能性有多大?

How likely are oscillations in a genetic feedback loop with delay?

作者信息

Cola Filippo, Marchetti Filippo, Tiana Guido

机构信息

Department of Physics and Center for Complexity and Biosystems, Università degli Studi di Milano and INFN, via Celoria 16, 20133, Milano, Italy.

Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, via Mario Bianco 9, 20131, Milan, Italy.

出版信息

Eur Phys J E Soft Matter. 2017 Aug;40(8):74. doi: 10.1140/epje/i2017-11563-y. Epub 2017 Aug 23.

Abstract

Some genetic control networks display temporal oscillations as a result of delays in their homeostatic control. A relevant question about these systems is whether the oscillating regime is a rare feature, or it corresponds to a sizeable volume of the space of parameters. The answer is not trivial mainly due to the large number of parameters controlling the rate equations which describe the network. We have developed an efficient sampling scheme of the parameter space, based on a Monte Carlo algorithm, and applied it to a two-node system with delay, characterised by a 8-dimension parameter space. The result is that the volume fraction of the parameter space associated with oscillations is small but not negligible, and it is weakly dependent on the duration of the delay. The most critical parameter to control oscillations is the coupling production rates, which must have opposite sign, giving rise to a negative feedback loop. The oscillating regions are connected except along the equilibrium constants between the two species, not allowing neutral evolution along this parameter.

摘要

一些基因控制网络由于其稳态控制中的延迟而呈现出时间振荡。关于这些系统的一个相关问题是,振荡状态是一种罕见的特征,还是对应于相当大的参数空间体积。答案并非显而易见,主要是因为控制描述该网络的速率方程的参数数量众多。我们基于蒙特卡罗算法开发了一种有效的参数空间采样方案,并将其应用于一个具有延迟的双节点系统,该系统的特征是具有一个8维参数空间。结果是,与振荡相关的参数空间体积分数很小但并非可以忽略不计,并且它对延迟持续时间的依赖性较弱。控制振荡的最关键参数是耦合产生率,它们必须具有相反的符号,从而产生一个负反馈回路。振荡区域是相连的,除了沿着两种物质之间的平衡常数方向,这使得沿着该参数无法进行中性进化。

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