Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods

BackgroundSeptic shock in children is an infectious disease caused by low immunity, and its mortality is very high. Early prediction of the risk of death in children with septic shock is helpful for clinicians to judge the severity of the disease, take active treatment measures, and improve the adve...

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Main Authors: Wei Guo, Hao Chen, Feng Wang, Yingjiao Chi, Wei Zhang, Shan Wang, Kezhu Chen, Hong Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1586584/full
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author Wei Guo
Hao Chen
Feng Wang
Yingjiao Chi
Wei Zhang
Shan Wang
Kezhu Chen
Hong Chen
author_facet Wei Guo
Hao Chen
Feng Wang
Yingjiao Chi
Wei Zhang
Shan Wang
Kezhu Chen
Hong Chen
author_sort Wei Guo
collection DOAJ
description BackgroundSeptic shock in children is an infectious disease caused by low immunity, and its mortality is very high. Early prediction of the risk of death in children with septic shock is helpful for clinicians to judge the severity of the disease, take active treatment measures, and improve the adverse outcomes of patients. However, the mechanism of death from sepsis in children remains unclear. This study aims to use bioinformatics and machine learning algorithms to identify key genes and pathways associated with fatal sepsis in children, and provide theoretical basis for rational drug use in follow-up TCM treatment.MethodsGene expression profiles were obtained from the GEO database (GSE4607) for 15 blank patients and 14 children with sepsis death. Differentially expressed genes (DEGs) were enriched by GO and KEGG pathways. Construct and visualize protein-protein interaction (PPI) networks to identify candidate genes responsible for fatal sepsis in children. Three kinds of machine learning models were established, and the candidate genes were screened by intersection to obtain the core genes with diagnostic value. ROC curve was drawn for core genes to clarify the diagnostic value of genetic markers.ResultsAnalysis of differences in the preprocessed dataset identified 83 genes, including 78 up-regulated genes and 5 down-regulated genes. 17 candidate genes were screened by protein interaction network analysis. Three machine learning algorithms LASSO, random forest (RF), and support vector machine recursive feature elimination (SVM-RFE) were used to finally screen out three core genes: CD163, MCEMP1 and RETN. CD163, MCEMP1 and RETN may jointly regulate complement and coagulation cascades, toll like receptor signaling pathway, graft versus host disease, type I diabetes mellitus.ConclusionIn this study, three core genes (CD163, MCEMP1 and RETN) that lead to sepsis death in children were screened out, providing a new understanding of the lethal mechanism of sepsis in children and a promising new therapeutic approach.
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publisher Frontiers Media S.A.
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spelling doaj-art-bdd646e36ac945c491f2d78b7bb12f962025-08-20T02:07:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15865841586584Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methodsWei Guo0Hao Chen1Feng Wang2Yingjiao Chi3Wei Zhang4Shan Wang5Kezhu Chen6Hong Chen7Department of Pediatrics, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, ChinaDepartment of Surgery, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, ChinaDepartment of Surgery, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, ChinaDepartment of Pediatrics, Harbin First Hospital, Harbin, ChinaDepartment of Pediatrics, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, ChinaNing ‘an Hospital of Traditional Chinese Medicine Pediatrics, Ning ‘an, ChinaGraduate School, Heilongjiang University of Chinese Medicine, Harbin, ChinaDepartment of Pediatrics, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, ChinaBackgroundSeptic shock in children is an infectious disease caused by low immunity, and its mortality is very high. Early prediction of the risk of death in children with septic shock is helpful for clinicians to judge the severity of the disease, take active treatment measures, and improve the adverse outcomes of patients. However, the mechanism of death from sepsis in children remains unclear. This study aims to use bioinformatics and machine learning algorithms to identify key genes and pathways associated with fatal sepsis in children, and provide theoretical basis for rational drug use in follow-up TCM treatment.MethodsGene expression profiles were obtained from the GEO database (GSE4607) for 15 blank patients and 14 children with sepsis death. Differentially expressed genes (DEGs) were enriched by GO and KEGG pathways. Construct and visualize protein-protein interaction (PPI) networks to identify candidate genes responsible for fatal sepsis in children. Three kinds of machine learning models were established, and the candidate genes were screened by intersection to obtain the core genes with diagnostic value. ROC curve was drawn for core genes to clarify the diagnostic value of genetic markers.ResultsAnalysis of differences in the preprocessed dataset identified 83 genes, including 78 up-regulated genes and 5 down-regulated genes. 17 candidate genes were screened by protein interaction network analysis. Three machine learning algorithms LASSO, random forest (RF), and support vector machine recursive feature elimination (SVM-RFE) were used to finally screen out three core genes: CD163, MCEMP1 and RETN. CD163, MCEMP1 and RETN may jointly regulate complement and coagulation cascades, toll like receptor signaling pathway, graft versus host disease, type I diabetes mellitus.ConclusionIn this study, three core genes (CD163, MCEMP1 and RETN) that lead to sepsis death in children were screened out, providing a new understanding of the lethal mechanism of sepsis in children and a promising new therapeutic approach.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1586584/fullseptic shockchildrenpotential geneinflammationmachine learning
spellingShingle Wei Guo
Hao Chen
Feng Wang
Yingjiao Chi
Wei Zhang
Shan Wang
Kezhu Chen
Hong Chen
Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods
Frontiers in Immunology
septic shock
children
potential gene
inflammation
machine learning
title Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods
title_full Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods
title_fullStr Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods
title_full_unstemmed Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods
title_short Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods
title_sort identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning methods
topic septic shock
children
potential gene
inflammation
machine learning
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1586584/full
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