Liu Wei, Li Dong, Zhang Jiyang, Zhu Yunping, He Fuchu
College of Mechanical & Electronic Engineering and Automatization, National University of Defense Technology, Changsha, China.
BMC Bioinformatics. 2006 Nov 27;7:515. doi: 10.1186/1471-2105-7-515.
Measuring each protein's importance in signaling networks helps to identify the crucial proteins in a cellular process, find the fragile portion of the biology system and further assist for disease therapy. However, there are relatively few methods to evaluate the importance of proteins in signaling networks.
We developed a novel network feature to evaluate the importance of proteins in signal transduction networks, that we call SigFlux, based on the concept of minimal path sets (MPSs). An MPS is a minimal set of nodes that can perform the signal propagation from ligands to target genes or feedback loops. We define SigFlux as the number of MPSs in which each protein is involved. We applied this network feature to the large signal transduction network in the hippocampal CA1 neuron of mice. Significant correlations were simultaneously observed between SigFlux and both the essentiality and evolutionary rate of genes. Compared with another commonly used network feature, connectivity, SigFlux has similar or better ability as connectivity to reflect a protein's essentiality. Further classification according to protein function demonstrates that high SigFlux, low connectivity proteins are abundant in receptors and transcriptional factors, indicating that SigFlux candescribe the importance of proteins within the context of the entire network.
SigFlux is a useful network feature in signal transduction networks that allows the prediction of the essentiality and conservation of proteins. With this novel network feature, proteins that participate in more pathways or feedback loops within a signaling network are proved far more likely to be essential and conserved during evolution than their counterparts.
衡量每种蛋白质在信号网络中的重要性有助于识别细胞过程中的关键蛋白质，找到生物系统的脆弱部分，并进一步辅助疾病治疗。然而，评估蛋白质在信号网络中重要性的方法相对较少。
我们基于最小路径集（MPSs）的概念开发了一种新的网络特征来评估蛋白质在信号转导网络中的重要性，我们将其称为SigFlux。一个MPS是一组最小的节点，能够执行从配体到靶基因或反馈回路的信号传播。我们将SigFlux定义为每种蛋白质所涉及的MPS的数量。我们将此网络特征应用于小鼠海马CA1神经元中的大型信号转导网络。同时观察到SigFlux与基因的必需性和进化速率之间存在显著相关性。与另一种常用的网络特征——连通性相比，SigFlux在反映蛋白质必需性方面具有与连通性相似或更好的能力。根据蛋白质功能进行的进一步分类表明，高SigFlux、低连通性的蛋白质在受体和转录因子中大量存在，这表明SigFlux能够在整个网络的背景下描述蛋白质的重要性。
SigFlux是信号转导网络中一种有用的网络特征，可用于预测蛋白质的必需性和保守性。有了这种新的网络特征，在信号网络中参与更多途径或反馈回路的蛋白质在进化过程中比其他蛋白质更有可能是必需的和保守的。
