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本研究旨在通过生物信息学方法筛选鉴定益气活血散干预脓毒症中的关键基因及预测核心通路。首先检索本草组鉴HERB平台获取益气活血散的成分和靶点，并通过多个疾病数据库检索筛选得到脓毒症的潜在靶点。通过STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络，利用PANTHER数据库对蛋白质进行分类注释；通过ChEA3平台预测转录因子并进行共表达模块分析；借助Network Analyst数据库构建转录因子与miRNA的互作网络；通过MSigDB数据库对基因进行可视化功能富集和通路注释分析；利用CytoHubba工具结合多重方法鉴定核心基因，并通过GEO数据库获得公共脓毒症数据集GSE28750和GSE54514,分别对核心基因表达矩阵进行验证和接收者操作特征曲线(receiver operating characteristic, ROC)分析。本研究共筛选出益气活血散中的21个活性成分，益气活血散干预脓毒症的8个核心基因。益气活血散治疗脓毒症的潜在治疗机制可能与HIF-1信号通路、 MARK信号通路和坏死性凋亡等信号途径相关；潜在相关生物过程有对含氧化合物反应、对细胞死亡的调节、对细胞因子的反应等。本研究通过生物信息学联合机器学习算法验证对核心基因的表达进行分析，加深了对益气活血散干预脓毒症的作用机制认识，并为中药治疗本病提供了潜在基因靶标及思路。
Abstract：This work used bioinformatics methods to screen for critical genes, and predict the primary pathways involved in sepsis. First, the Materia Medica HERB platform was explored to find the ingredients and targets of Yiqi Huoxue powder. Afterward, several illness registries were used to screen for conceivable relevant targets of sepsis. The STRING database was used to construct the protein-protein interaction(PPI) network; PANTHER was used to annotate proteins; ChEA3 platform was used to predict transcription factors and analyze co-expression modules; Network Analyst database was utilized to create the interaction network between transcription factors and miRNA. The MSigDB database was used to visualize the functional enrichment and pathway annotation analysis of genes. Using CytoHubba as a platform to construct the hub gene expression matrix. The receiver operating characteristic(ROC) curve was produced for analysis, and the hub gene regulation grid was identified using this platform. The public sepsis samples GSE28750 and GSE54514 were obtained via the GEO database. Eight hub genes and a total of twenty-one active components were evaluated in this investigation for the intervention of sepsis. Yiqi Huoxue powder may have a beneficial impact on sepsis by means of pathways such as the HIF-1 signaling pathway, MARK signaling pathway, necroptosis, etc. Effective biological processes that may be involved in the response to oxygen containing compound, regulation of cell death, and response to cytokine. By employing bioinformatics and machine learning models validation methods of analyzing the expression of core genes, this study advanced the comprehension of Yiqi Huoxue powder′s mechanism of action in managing sepsis. Furthermore, the study identified potential gene targets and proposed ideas for treating sepsis with traditional Chinese medicine.
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基本信息:
DOI：10.13417/j.gab.043.001469
中图分类号:R278
引用信息:
[1]邓雅文,曾瑞峰,徐艺萌,等.益气活血散干预脓毒症关键基因和核心通路的生物信息学研究[J].基因组学与应用生物学,2024,43(08):1469-1482.DOI:10.13417/j.gab.043.001469.
基金信息:
广东省自然科学基金面上项目(2020A1515010512); 广东省中医院临床研究专项(YN10101908); 广东省中医急症研究重点实验室(2023B1212060062)共同资助
2024-05-21
2024-05-21
2024-05-21