Network-based analysis of blood metabolic biomarkers for stroke
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摘要: 目的 利用网络分析方法整合已报道的脑卒中相关临床血液代谢物的相关文献,探索新的潜在标志物和疾病作用靶点。 方法 搜集整理采用代谢组学方法分析脑卒中临床血液样本的文献,按照缺血性脑卒中(IS)和出血性脑卒中(HS)2个大类提取差异代谢物; 采用代谢通路富集分析方法,分别解析与IS和HS关系密切的代谢途径。在此基础上,采用网络拓扑分析方法构建脑卒中相关“代谢物-通路”作用网络模块,以节点中心性为指标筛选核心代谢通路和代谢标志物。 结果 分别获得与IS和HS相关的代谢物117个和11个; 发现13条和12条代谢途径在IS发生前后出现显著改变; 发现19条代谢途径在HS发生后出现显著变化。经网络分析,筛选出了与IS发生发展密切关联的核心代谢通路12条、代谢物标志物47个,包括氨回收、尿素循环等通路以及支链氨基酸、谷氨酸等物质。 结论 机体代谢异常与脑卒中的发生、发展密切相关。Abstract: Objective To explore new potential markers and disease targets of stroke by integrating and analyzing the literature reporting metabolites of stroke in the guidance of the network analgsis method. Methods Differential metabolites found by clinical metabolomics studies of stroke were collected and summarized according to the two major categories of ischemic stroke(IS)and hemorrhagic stroke(HS). The pathway enrichment analysis was performed to analyze the metabolic pathways closely related to IS and HS, respectively. On this basis, the network topology analysis was employed to construct a stroke-related "metabolite-pathway" interaction network, and the key metabolic pathways and metabolic markers were screened out with the node centrality as an indicator. Results Totally 117 and 11 potential markers related to IS and HS were obtained, respectively. A total of 13 and 12 metabolic pathways were found to be significantly changed before and after the onset of IS, respectively, by the metabolic pathway analysis, while 19 metabolic pathways that related to HS were uncovered by the joint pathway analysis. Finally, 12 key metabolic pathways and 47 metabolite markers such as ammonia recycling, urea cycle, branched-chain amino acids, and glutamic acid were uncovered by the network analysis. Conclusion Metabolic disorders have a close relationship with the development and progression of stroke.
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Keywords:
- stroke /
- biomarkers /
- metabolomics /
- network /
- blood
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