Control of Intracellular Molecular Networks Using Algebraic Methods.
Control of Intracellular Molecular Networks Using Algebraic Methods.
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DOI：
10.1007/s11538-019-00679-w
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发表时间：
2019-12-23
影响因子：
3.5
通讯作者：
Murrugarra D
中科院分区：
文献类型：
--
作者：
Sordo Vieira L;Laubenbacher RC;Murrugarra D
生物学和医学中的许多问题都有控制的成分。通常，目标可能是修改细胞内网络，如基因调控网络或信号网络，以便细胞获得某种表型，这在癌症中发生。如果网络是由数学模型表示的，数学控制方法是可用的，如常微分方程组，那么这个问题可能会得到系统的解决。这种方法也适用于其他一些模型类型，如布尔网络，其中已经开发了基于结构的方法，以及稳定的基序技术。然而，越来越多的离散模型是混合状态或多状态的，也就是说，一些或所有变量有两个以上的状态，因此需要发展的控制策略，多态网络。本文提出了一种控制方法，广泛适用于一般的多状态模型的基础上编码多项式动力系统在有限的代数状态集，并使用计算代数找到适当的干预策略。为了证明这种方法的可行性和适用性，我们将其应用到最近开发的E2F介导的膀胱癌生长的多状态细胞内模型和连接细胞内铁代谢和致癌途径的模型。这些已发表的模型确定的控制策略在某些情况下是新颖的，代表新的假设，或在其他文献中作为潜在的药物靶点。我们用于查找控制策略的Macaulay2脚本可通过GitHub在https://github.com/luissv7/multistatepdscontrol上公开获取。
Many problems in biology and medicine have a control component. Often, the goal might be to modify intracellular networks, such as gene regulatory networks or signaling networks, in order for cells to achieve a certain phenotype, what happens in cancer. If the network is represented by a mathematical model for which mathematical control approaches are available, such as systems of ordinary differential equations, then this problem might be solved systematically. Such approaches are available for some other model types, such as Boolean networks, where structure-based approaches have been developed, as well as stable motif techniques. However, increasingly many published discrete models are mixed-state or multistate, that is, some or all variables have more than two states, and thus the development of control strategies for multistate networks is needed. This paper presents a control approach broadly applicable to general multistate models based on encoding them as polynomial dynamical systems over a finite algebraic state set, and using computational algebra for finding appropriate intervention strategies. To demonstrate the feasibility and applicability of this method, we apply it to a recently developed multistate intracellular model of E2F-mediated bladder cancerous growth and to a model linking intracellular iron metabolism and oncogenic pathways. The control strategies identified for these published models are novel in some cases and represent new hypotheses, or are supported by the literature in others as potential drug targets. Our Macaulay2 scripts to find control strategies are publicly available through GitHub at https://github.com/luissv7/multistatepdscontrol.
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影响因子：
4.3
作者：
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影响因子：
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作者：
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通讯作者：
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