Systematic reverse engineering of network topologies: a case study of resettable bistable cellular responses.
Systematic reverse engineering of network topologies: a case study of resettable bistable cellular responses.
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DOI：
10.1371/journal.pone.0105833
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xing J
中科院分区：
文献类型：
--
作者：
Mondal D;Dougherty E;Mukhopadhyay A;Carbo A;Yao G;Xing J
系统生物学的一个重点主题是揭示生物网络的设计原理，即特定的网络结构如何产生特定的系统特性。为此，我们之前开发了一种逆向工程程序来识别极有可能生成所需系统属性的网络拓扑。我们的方法搜索网络拓扑集合的连续参数空间，而无需像其他逆向工程过程中传统的做法那样单独枚举各个网络拓扑。在这里，我们在先前研究的问题上测试了这种 CPSS（连续参数空间搜索）方法：Rb-E2F 基因网络在调节哺乳动物细胞的静止到增殖转变中的可重置双稳态。从简化的 Rb-E2F 基因网络中，我们确定了负责产生可重置双稳态的网络拓扑。 CPSS识别的拓扑与之前基于个体拓扑搜索（ITS）的研究报告的拓扑一致，证明了CPSS方法的有效性。由于 CPSS 和 ITS 搜索基于不同的数学公式和不同的算法，因此结果的一致性也有助于交叉验证这两种方法。 CPSS 方法的独特优势在于其适用于具有大量节点的生物网络。为了帮助将 CPSS 方法应用于其他生物系统的研究，我们开发了一个计算机软件包，可在信息 S1 中找到。
A focused theme in systems biology is to uncover design principles of biological networks, that is, how specific network structures yield specific systems properties. For this purpose, we have previously developed a reverse engineering procedure to identify network topologies with high likelihood in generating desired systems properties. Our method searches the continuous parameter space of an assembly of network topologies, without enumerating individual network topologies separately as traditionally done in other reverse engineering procedures. Here we tested this CPSS (continuous parameter space search) method on a previously studied problem: the resettable bistability of an Rb-E2F gene network in regulating the quiescence-to-proliferation transition of mammalian cells. From a simplified Rb-E2F gene network, we identified network topologies responsible for generating resettable bistability. The CPSS-identified topologies are consistent with those reported in the previous study based on individual topology search (ITS), demonstrating the effectiveness of the CPSS approach. Since the CPSS and ITS searches are based on different mathematical formulations and different algorithms, the consistency of the results also helps cross-validate both approaches. A unique advantage of the CPSS approach lies in its applicability to biological networks with large numbers of nodes. To aid the application of the CPSS approach to the study of other biological systems, we have developed a computer package that is available in Information S1.
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影响因子：
4.3
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
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作者：
Fu, Yan;Jiang, Xiaoshan;Xing, Jianhua
通讯作者：
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