Inverse bifurcation analysis: application to simple gene systems.

Inverse bifurcation analysis: application to simple gene systems.
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逆分叉分析:应用于简单基因系统。

DOI:
10.1186/1748-7188-1-11
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发表时间:
2006-07-21
期刊:
Algorithms for molecular biology : AMB
影响因子:
--
通讯作者:
Schuster P
Schuster P
中科院分区:
其他
文献类型:
--
作者:
Lu J;Engl HW;Schuster P

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分叉分析已被证明是理解基因调控网络定性行为的一种有力方法。除了确定从参数空间到模型行为空间的映射的更传统的正问题之外,确定模型参数以导致分叉图的某些期望性质的逆问题提供了用于解决重要生物学问题的有吸引力的方法。这些包括理解定性行为的鲁棒性如何从系统设计中产生,以及提供一种方法来设计具有定性特性的生物网络。我们证明了某些生物学意义上的逆分叉问题可以转换为涉及参考参数集到分叉流形的最小距离的优化问题。该公式允许基于执行一系列特征系统计算和单参数连续解的迭代求解过程,后者是现有数值分叉软件的标准功能。作为所提出的方法的应用,我们表明,最大化区域的一个给定的定性行为,以及反向工程的基因开关的问题可以建模和有效地解决。
Bifurcation analysis has proven to be a powerful method for understanding the qualitative behavior of gene regulatory networks. In addition to the more traditional forward problem of determining the mapping from parameter space to the space of model behavior, the inverse problem of determining model parameters to result in certain desired properties of the bifurcation diagram provides an attractive methodology for addressing important biological problems. These include understanding how the robustness of qualitative behavior arises from system design as well as providing a way to engineer biological networks with qualitative properties. We demonstrate that certain inverse bifurcation problems of biological interest may be cast as optimization problems involving minimal distances of reference parameter sets to bifurcation manifolds. This formulation allows for an iterative solution procedure based on performing a sequence of eigen-system computations and one-parameter continuations of solutions, the latter being a standard capability in existing numerical bifurcation software. As applications of the proposed method, we show that the problem of maximizing regions of a given qualitative behavior as well as the reverse engineering of bistable gene switches can be modelled and efficiently solved.
DOI: 10.1093/bioinformatics/bth110
发表时间: 2004-07-01
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影响因子: 5.8
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