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帕金森病的病因病机复杂且不清楚,遗传因素发挥的作用在帕金森的发生发展中不可或缺。本研究从NCBI数据库搜索帕金森病的致病基因668个,使用String构建并可视化帕金森病基因网络,得到一个614个节点,9 376条边的中心放射性网状网络。然后使用3种Cytoscape中常用的划模块插件将帕金森病基因网络划分成模块网络,通过网络结构熵来评价模块的稳定性,结果发现MCODE cluster划分的15个模块熵值最小,为4.166 79。使用DAVID数据库分别对帕金森病基因网络和模块网络进行功能富集分析,分别得到76条和100条通路,有69条重叠通路,覆盖率高达90.79%。通过模块富集结果发现了31条PD的新的可能的通路,使用PubMed数据对这与帕金森病关联的31条通路进行文献验证,发现23 (74.2%)条通路已被文章证明与帕金森疾病有关,8条未验证通路或将成为下一步探索和研究的重点。本研究体现出模块分析尽管筛选掉一些基因靶点,但大部分的生物学功能被保留,并且会发现潜在的相关通路。模块的优越性也为后期疾病与药物的关联提供依据,是中药选择和新药开发的前行探索。
Abstract：The etiology and pathogenesis of Parkinson's disease are complex and unclear. The role of genetic factors is indispensable in the occurrence and development of Parkinson's disease. In our study, we searched 668 related genes of Parkinson's disease from the NCBI database, constructed and visualized the Parkinson's disease gene network by String database, and obtained a central radioactive mesh network with 614 nodes and 9 376 edges.Then three kinds of divided module plug-ins in Cytoscape were used to divide the Parkinson's disease gene network into module networks, and evaluated the stability of the module through the network structure entropy. The result showed that the 15 modules divided by the MCODE cluster had the smallest entropy value of 4.16 679. Used the DAVID database to perform functional enrichment analysis on the Parkinson's disease gene network and the module network respectively, we obtained 76 and 100 pathways, with 69 overlapping pathways, and the coverage rate was as high as 90.79%. Through enrichment analysis of module, we found 31 new possible pathways, used PubMed data to validate the 31 pathways associated with Parkinson's disease, and found that 23(74.2%) pathways have been proved by the article to be related to Parkinson's disease, and 8 unverified pathways may become the focus of exploration and research in the next step. This study suggested that although some gene targets have been screened out by module analysis, most of the biological functions are preserved and potential related pathways will be discovered. The superiority of the module also provides a basis for the association of later diseases and drugs,and is a forward exploration of traditional Chinese medicine selection and new drug development.
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基本信息:
DOI：10.13417/j.gab.040.002382
中图分类号:R742.5
引用信息:
[1]陈亚飞,刘琼,刘骏,等.通过整合基因、网络、模块关系分析帕金森病生物学机制[J].基因组学与应用生物学,2021,40(Z1):2382-2388.DOI:10.13417/j.gab.040.002382.
基金信息:
国家科技部重大专项(重大新药创制)(2017ZX09301059)资助
2020-06-15
2020-06-15
2020-06-15