Finding Instability in Biological Models
Finding Instability in Biological Models
复制标题
发现生物模型中的不稳定性
DOI：
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Nir Piterman
中科院分区：
文献类型：
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作者：
Byron Cook;J. Fisher;B. Hall;Samin S. Ishtiaq;Garvit Juniwal;Nir Piterman
生物模型的稳定性是建立其可靠性和准确性的重要测试。生物系统的稳定性代表了一个强大的系统总是恢复到稳态的能力。在最近的工作中，已经发现用于证明稳定性的模块化方法是快速和可扩展的。然而，如果稳定性未被证明，则当前可用的技术应用通过不稳定状态空间的穷举搜索来找到循环。这种搜索通常在计算上非常昂贵，限制了其实用性。在这里，我们提出了一种新的模块化方法，消除了对循环的穷举搜索的需要。使用生物系统的模型，我们表明，该技术发现循环显着快于蛮力的方法。此外，对于一个子集的稳定系统，这是抵抗模块化的证明，我们观察到的速度高达3个数量级的穷举搜索循环，避免了不稳定。与我们的新程序，我们能够证明不稳定性和稳定性，在一些现实的生物模型，包括适应细菌的趋化性，λ噬菌体溶源性/裂解开关，电压门控通道开放和cAMP振荡的黏菌Dictyosteelium discoideum。这种新方法将支持生物医学新工具的开发。
The stability of biological models is an important test for establishing their soundness and accuracy. Stability in biological systems represents the ability of a robust system to always return to homeostasis. In recent work, modular approaches for proving stability have been found to be swift and scalable. If stability is however not proved, the currently available techniques apply an exhaustive search through the unstable state space to find loops. This search is frequently prohibitively computationally expensive, limiting its usefulness. Here we present a new modular approach eliminating the need for an exhaustive search for loops. Using models of biological systems we show that the technique finds loops significantly faster than brute force approaches. Furthermore, for a subset of stable systems which are resistant to modular proofs, we observe a speed up of up to 3 orders of magnitude as the exhaustive searches for loops which cause instability are avoided. With our new procedure we are able to prove instability and stability in a number of realistic biological models, including adaptation in bacterial chemotaxis, the lambda phage lysogeny/lysis switch, voltage gated channel opening and cAMP oscillations in the slime mold Dictyostelium discoideum. This new approach will support the development of new tools for biomedicine.
髓系祖细胞的分层分化由转录因子网络编码。
影响因子：
3.7
作者：
Krumsiek J;Marr C;Schroeder T;Theis FJ
通讯作者：
Theis FJ