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采用 Hill 函数对开关型基因响应进行随机基因表达建模。

Stochastic gene expression modeling with Hill function for switch-like gene responses.

机构信息

Department of Electrical and Electronic Engineering, Imperial College London, South Kensington Campus, London SW7 2BT, United Kingdom.

出版信息

IEEE/ACM Trans Comput Biol Bioinform. 2012 Jul-Aug;9(4):973-9. doi: 10.1109/TCBB.2011.153.

Abstract

Gene expression models play a key role to understand the mechanisms of gene regulation whose aspects are grade and switch-like responses. Though many stochastic approaches attempt to explain the gene expression mechanisms, the Gillespie algorithm which is commonly used to simulate the stochastic models requires additional gene cascade to explain the switch-like behaviors of gene responses. In this study, we propose a stochastic gene expression model describing the switch-like behaviors of a gene by employing Hill functions to the conventional Gillespie algorithm. We assume eight processes of gene expression and their biologically appropriate reaction rates are estimated based on published literatures. We observed that the state of the system of the toggled switch model is rarely changed since the Hill function prevents the activation of involved proteins when their concentrations stay below a criterion. In ScbA-ScbR system, which can control the antibiotic metabolite production of microorganisms, our modified Gillespie algorithm successfully describes the switch-like behaviors of gene responses and oscillatory expressions which are consistent with the published experimental study.

摘要

基因表达模型在理解基因调控机制方面起着关键作用,其方面包括级联和开关样反应。尽管许多随机方法试图解释基因表达机制,但常用的模拟随机模型的 Gillespie 算法需要额外的基因级联来解释基因反应的开关样行为。在这项研究中,我们通过将 Hill 函数应用于传统的 Gillespie 算法,提出了一个描述基因开关样行为的随机基因表达模型。我们假设了八个基因表达过程,并且根据已发表的文献估计了它们的生物学适当反应速率。我们观察到,由于 Hill 函数在涉及蛋白质的浓度低于标准时防止其激活,因此 toggle 开关模型的系统状态很少改变。在可以控制微生物抗生素代谢产物产生的 ScbA-ScbR 系统中,我们改进的 Gillespie 算法成功地描述了基因反应的开关样行为和与已发表的实验研究一致的振荡表达。

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