Pathway enrichment analysis approach based on topological structure and updated annotation of pathway
Pathway enrichment analysis approach based on topological structure and updated annotation of pathway
复制标题
基于路径拓扑结构和更新注释的路径富集分析方法。
DOI：
10.1093/bib/bbx091
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发表时间：
2019-01-01
影响因子：
9.5
通讯作者：
Jiang，Wei
中科院分区：
文献类型：
--
作者：
Yang，Qian;Wang，Shuyuan;Jiang，Wei
途径富集分析已被广泛应用于识别癌症风险途径，并有助于阐明肿瘤发生的机制。然而，现有的方法大多使用过时的途径信息，忽略了途径中复杂的基因相互作用。本文首先简要回顾了目前广泛应用的途径富集分析方法，然后提出了一种新的基于拓扑结构的途径富集分析（TPEA）方法，该方法综合了途径中基因的拓扑结构和全局上下游位置。我们通过分析三种肿瘤类型（结直肠癌、甲状腺癌和子宫内膜癌）的六种基因表达谱，将TPEA与四种广泛使用的途径富集分析工具进行比较，包括注释、可视化和集成发现数据库（大卫）、基因集富集分析（GSEA）、基于中心性的途径富集（CePa）和信号通路影响分析（SPIA）。因此，我们确定了几个已知的癌症风险途径，这些途径是现有工具无法获得的，并且在分析同一癌症的不同数据集时，TPEA的结果比其他工具更稳定。最终，我们开发了一个R包来实现TPEA，它可以在线更新KEGG途径信息，并可在综合R档案网络（CRAN）上获取：https://cran.r-project.org/web/packages/TPEA/。
Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/.