利用混合系统理论在分子水平上模拟治疗和药物效应

Xiangfang Li, Lijun Qian, E. Dougherty
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引用次数: 3

摘要

在本文中,我们建议在分子水平上使用混合系统模型来研究治疗和药物效应。具体来说,我们提出了一个通用的分段线性模型来分析药物对基因调控网络中基因状态的影响。我们打算回答以下问题:给定一个初始状态,治疗或药物(控制输入)是否会将目标基因驱动到一个没有治疗或药物无法达到的新状态?假设药物的浓度水平保持不变。换句话说,我们试图确定是否有机会治疗或药物将有效地改变基因表达。我们对两个案例进行了详细的分析。在第一种情况下,只有一个靶基因;而在第二种情况下,还有另一个基因与目标基因相互作用。推导了(基因调控网络和药物设计)各参数与受控基因的收敛和稳定状态之间的关系,并对其进行了详细的讨论。利用MATLAB/SIMULINK进行了仿真,结果证实了我们的分析结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modeling treatment and drug effects at the molecular level using hybrid system theory
In this paper, we propose to study the treatment and drug effects at the molecular level using a hybrid system model. Specifically, we propose a generic piecewise linear model to analyze drug effects on the state of the genes in a genetic regulatory network. We intend to answer the following question: given an initial state, would a treatment or drug (control input) drive the target gene to a new desired state that are not reachable without the treatment or drug? assuming that the concentration level of the drug remains constant. In other words, we try to identify whether there is a chance that the treatment or drug will be effective for changing gene expressions at all. We provide detailed analysis for two cases. In the first case, there is only one target gene; while in the second case, there is also another gene interacting with the target gene. The relationships between various parameters (of the genetic regulatory network and the design of the drug) and the convergence and the steady state of the controlled genes are derived analytically and discussed in detail. Simulations are performed using MATLAB/SIMULINK and the results confirmed our analytical findings.
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