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生物信息学联合机器学习鉴定重症登革热的预警标志物OA北大核心CSTPCD

Bioinformatics combined with machine learning to identify early warning markers for severe dengue

中文摘要英文摘要

目的 基于生物信息学联合机器学习鉴定重症登革热的预警标志物,探讨临床重症登革热发生风险的评价体系.方法 通过基因表达综合(GEO)数据库分析普通登革热与重症登革热患者的差异表达基因,并进行基因本体论(GO)、京都基因与基因组数据库(KEGG)富集分析;通过随机森林模型筛选重症登革热预警基因,并利用受试者操作特征(ROC)曲线验证基因的准确性;最后采用列线图对预警基因进行量化,通过预警基因的表达量预测普通登革热进展为重症登革热的风险.结果 共获得817个差异表达基因,抗微生物体液反应、体液免疫反应、丝氨酸水解酶活性和花生四烯酸代谢等生物过程可能与重症登革热的发生发展密切相关;筛选出AZU1、PDCD4、COL4A3BP、TRPM4、ATP4A 5个重症登革热预警基因,其中ATP4A、COL4A3BP、TRPM4呈低表达,而AZU1、PDCD4呈高表达,ROC曲线提示基因准确性良好;列线图提示模型预测准确度、临床获益率、临床有效性均良好.结论 测定AZU1、PDCD4、COL4A3BP、TRPM4、ATP4A 5个预警基因的表达量有助于评估重症登革热的发生风险.

Objective The goals of this study were to identify early warning markers of severe dengue based on bioinformatics com-bined with machine learning,and explore the evaluation system of the risk of occurrence of severe dengue.Methods Based on the Gene Expression Omnibus database,the differentially expressed genes between dengue and severe dengue were analyzed,and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted.Early warning genes of severe dengue were screened using a random forest model,and the accuracy of the genes was verified using receiver operating characteristic(ROC)curves.Finally,nomograms were constructed to quantify the warning genes and predict the risk of progression from dengue to severe dengue based on the expression level of these genes.Results A total of 817 differentially expressed genes were identified,along with the associated biolo-gical processes that may be closely related to the occurrence and development of severe dengue,namely,antimicrobial humoral response,humoral immune response,serine hydrolase activity,and arachidonic acid metabolism.Based on this analysis,five early warning genes were isolated:AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A.Among these,ATP4A,COL4A3BP,and TRPM4 showed low expression levels,whereas AZU1and PDCD4were highly expressed.The ROC curves indicated that these genes were accurate pre-dictors of severe dengue.The nomograms indicated good predictive accuracy,clinical benefit rate,and clinical effectiveness of the model.Conclusion Measuring the expression levels of five warning genes(AZU1,PDCD4,COL4A3BP,TRPM4,and ATP4A)may help to evaluate the risk of severe dengue.

谢铱子;詹少锋;黄慧婷;温武金;刘小虹;江勇

深圳市中西医结合医院肺病科/呼吸与危重症医学科,广东 深圳 518104||广州中医药大学第一临床医学院,广州 510405||广州中医药大学第一附属医院呼吸与危重症医学科,广州 510405||广州中医药大学岭南医学研究中心,广州 510405||广东省中医临床研究院,广州 510405广州中医药大学第一附属医院呼吸与危重症医学科,广州 510405||广东省中医临床研究院,广州 510405深圳市中西医结合医院肺病科/呼吸与危重症医学科,广东 深圳 518104

临床医学

重症登革热预警基因生物过程风险评估

severe denguewarninggenebiological processrisk assessment

《中国医科大学学报》 2024 (007)

583-590 / 8

国家自然科学基金(82274418);广东省重点领域研发计划项目(2020B1111100002);广东省重点科室(中西医协同科室)建设项目;深圳市"医疗卫生三名工程"建设项目(SZZYSM202206013);深圳市宝安区医疗卫生科研项目(2023JD107);广州市科技计划(2023A04J1168)

10.12007/j.issn.0258-4646.2024.07.002

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