Li Xianbin, Shen Liangzhong, Shang Xuequn, Liu Wenbin
Department of Physics and Electronic information engineering, Wenzhou University,Wenzhou, Zhejiang, China.
School of Computer Science and Technology, Northwestern Polytechnical University, Xi'an, China.
PLoS One. 2015 Jul 24;10(7):e0132813. doi: 10.1371/journal.pone.0132813. eCollection 2015.
Pathway analysis is a common approach to gain insight from biological experiments. Signaling-pathway impact analysis (SPIA) is one such method and combines both the classical enrichment analysis and the actual perturbation on a given pathway. Because this method focuses on a single pathway, its resolution generally is not very high because the differentially expressed genes may be enriched in a local region of the pathway. In the present work, to identify cancer-related pathways, we incorporated a recent subpathway analysis method into the SPIA method to form the "sub-SPIA method." The original subpathway analysis uses the k-clique structure to define a subpathway. However, it is not sufficiently flexible to capture subpathways with complex structure and usually results in many overlapping subpathways. We therefore propose using the minimal-spanning-tree structure to find a subpathway. We apply this approach to colorectal cancer and lung cancer datasets, and our results show that sub-SPIA can identify many significant pathways associated with each specific cancer that other methods miss. Based on the entire pathway network in the Kyoto Encyclopedia of Genes and Genomes, we find that the pathways identified by sub-SPIA not only have the largest average degree, but also are more closely connected than those identified by other methods. This result suggests that the abnormality signal propagating through them might be responsible for the specific cancer or disease.
通路分析是从生物学实验中获取见解的常用方法。信号通路影响分析(SPIA)就是这样一种方法,它结合了经典的富集分析和对给定通路的实际扰动。由于该方法专注于单个通路,其分辨率通常不是很高,因为差异表达基因可能富集在通路的局部区域。在本研究中,为了识别癌症相关通路,我们将一种最新的子通路分析方法纳入SPIA方法中,形成了“子SPIA方法”。原始的子通路分析使用k-团结构来定义子通路。然而,它在捕获具有复杂结构的子通路方面不够灵活,并且通常会导致许多重叠的子通路。因此,我们建议使用最小生成树结构来寻找子通路。我们将这种方法应用于结直肠癌和肺癌数据集,结果表明子SPIA可以识别出许多与每种特定癌症相关的重要通路,而其他方法则会遗漏这些通路。基于京都基因与基因组百科全书中的整个通路网络,我们发现子SPIA识别出的通路不仅平均度最大,而且比其他方法识别出的通路连接更紧密。这一结果表明,通过它们传播的异常信号可能是特定癌症或疾病的原因。