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Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning

摘要Background Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dys-regulated host response to infection in children.It is associated with high rates of morbidity and mortality,and rapid detec-tion and administration of antimicrobials have been emphasized.The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness.Methods Three gene expression datasets were available from the Gene Expression Omnibus collection.First,the differen-tially expressed genes(DEGs)were found with the use of the R program,and then gene set enrichment analysis was carried out.Subsequently,the DEGs were combined with the major module genes chosen using the weighted gene co-expression network.The hub genes were identified by the use of three machine-learning algorithms:random forest,support vector machine-recursive feature elimination,and least absolute shrinkage and selection operator.The receiver operating char-acteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes.In addition,the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT).The relationship between the diagnostic markers and infiltrating immune cells was further studied.Results Overall,after overlapping key module genes and DEGs,we detected 402 overlapping genes.As pediatric sepsis diagnostic indicators,CYSTM1(AUC=0.988),MMP8(AUC=0.973),and CD 177(AUC=0.986)were investigated and demonstrated statistically significant differences(P<0.05)and diagnostic efficacy in the validation set.As indicated by the immune cell infiltration analysis,multiple immune cells may be involved in the development of pediatric sepsis.Addition-ally,all diagnostic characteristics may correlate with immune cells to varying degrees.Conclusions The candidate hub genes(CD177,CYSTM1,and MMP8)were identified,and the nomogram was constructed for pediatric sepsis diagnosis.Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

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作者 Wen-Yuan Zhang [1] Zhong-Hua Chen [2] Xiao-Xia An [1] Hui Li [1] Hua-Lin Zhang [1] Shui-Jing Wu [1] Yu-Qian Guo [1] Kai Zhang [3] Cong-Li Zeng [1] Xiang-Ming Fang 学术成果认领
作者单位 Department of Anesthesiology and Intensive Care,School of Medicine,The First Affiliated Hospital,Zhejiang University,QingChun Road 79,Hangzhou 310003,China [1] Department of Anesthesiology and Intensive Care,School of Medicine,The First Affiliated Hospital,Zhejiang University,QingChun Road 79,Hangzhou 310003,China;Department of Anesthesiology,Shaoxing People's Hospital(Shaoxing Hospital,Zhejiang University School of Medicine),Shaoxing 312000,China [2] Department of Anesthesiology,Vagelos College of Physicians and Surgeons,Columbia University,New York,NY,USA [3]
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DOI 10.1007/s12519-023-00717-7
发布时间 2023-12-22(万方平台首次上网日期,不代表论文的发表时间)
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