A network-based pathway-expanding approach for pathway analysis.
A network-based pathway-expanding approach for pathway analysis.
复制标题
一种基于网络的路径扩展方法用于路径分析
DOI：
10.1186/s12859-016-1333-x
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发表时间：
2016-12-23
影响因子：
3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhang Q;Li J;Xie H;Xue H;Wang Y
结合基因组学和蛋白质组学等多种高通量数据的通路分析已成为深入了解复杂疾病发病机制的首选方法。目前，已经开发了几种通路分析方法来研究复杂疾病。然而，这些方法没有考虑通路内部和外部基因之间以及通路之间的相互作用。因此，这些方法仍然面临一些挑战。在此，我们提出一种基于网络的通路扩展方法，该方法考虑了生物网络的拓扑结构。
首先，整合蛋白质 - 蛋白质相互作用（PPI）信息、基因表达数据和通路数据库构建两个加权基因 - 基因相互作用网络（肿瘤和正常）。然后，通过检测两个加权网络中扩展通路拓扑结构的差异来识别显著通路。将所提出的方法用于分析两组乳腺癌数据。结果，使用该方法识别出的前15条通路得到了已发表文献和其他方法的生物学知识的支持。此外，还将该方法与其他方法（如GSEA和SPIA）进行了比较，并使用前15条扩展通路的分类性能进行了评估。
提出了一种新的基于网络的通路扩展方法以避免现有通路分析方法的局限性。实验结果表明，该方法能够准确、可靠地识别与相应疾病相关的显著通路。
本文的在线版本（doi:10.1186/s12859 - 016 - 1333 - x）包含补充材料，授权用户可获取。
BackgroundPathway analysis combining multiple types of high-throughput data, such as genomics and proteomics, has become the first choice to gain insights into the pathogenesis of complex diseases. Currently, several pathway analysis methods have been developed to study complex diseases. However, these methods did not take into account the interaction between internal and external genes of the pathway and between pathways. Hence, these approaches still face some challenges. Here, we propose a network-based pathway-expanding approach that takes the topological structures of biological networks into account.ResultsFirst, two weighted gene-gene interaction networks (tumor and normal) are constructed integrating protein-protein interaction(PPI) information, gene expression data and pathway databases. Then, they are used to identify significant pathways through testing the difference of topological structures of expanded pathways in the two weighted networks. The proposed method is employed to analyze two breast cancer data. As a result, the top 15 pathways identified using the proposed method are supported by biological knowledge from the published literatures and other methods. In addition, the proposed method is also compared with other methods, such as GSEA and SPIA, and estimated using the classification performance of the top 15 expanded pathways.ConclusionsA novel network-based pathway-expanding approach is proposed to avoid the limitations of existing pathway analysis approaches. Experimental results indicate that the proposed method can accurately and reliably identify significant pathways which are related to the corresponding disease.