Optimal control of gene regulatory networks with effectiveness of multiple drugs: a Boolean network approach.
Optimal control of gene regulatory networks with effectiveness of multiple drugs: a Boolean network approach.
复制标题
DOI：
10.1155/2013/246761
复制
发表时间：
2013
影响因子：
--
通讯作者：
Hiraishi K
中科院分区：
文献类型：
--
作者：
Kobayashi K;Hiraishi K
基因调控网络控制理论的发展是系统生物学领域的重要课题之一，其成果有望在未来应用于基因治疗技术。本文研究了一种基于布尔网络（BN）的控制方法。A BN被广泛用作基因调控网络的模型，基因表达用二值（0或1）表示。在控制问题中，我们假设某一部分基因的浓度水平是任意确定的作为控制输入。然而，在某些情况下，不存在满足这一假设的基因，因此考虑通过外部刺激进行结构控制是很重要的。此外，这些控制是通过多种药物来实现的，同时也要考虑到作用持续时间和副作用等多重效应。在本文中，我们提出了一种具有两种控制输入的BN模型和一种具有药物有效性持续时间的最优控制方法。首先，讨论了BN模型和药物有效性持续时间。其次，将最优控制问题化为整数线性规划问题。最后进行了数值模拟。
Developing control theory of gene regulatory networks is one of the significant topics in the field of systems biology, and it is expected to apply the obtained results to gene therapy technologies in the future. In this paper, a control method using a Boolean network (BN) is studied. A BN is widely used as a model of gene regulatory networks, and gene expression is expressed by a binary value (0 or 1). In the control problem, we assume that the concentration level of a part of genes is arbitrarily determined as the control input. However, there are cases that no gene satisfying this assumption exists, and it is important to consider structural control via external stimuli. Furthermore, these controls are realized by multiple drugs, and it is also important to consider multiple effects such as duration of effect and side effects. In this paper, we propose a BN model with two types of the control inputs and an optimal control method with duration of drug effectiveness. First, a BN model and duration of drug effectiveness are discussed. Next, the optimal control problem is formulated and is reduced to an integer linear programming problem. Finally, numerical simulations are shown.