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Identifying potential three key targets gene for septic shock in children using bioinformatics and machine learning
Wei Guo1, Hao Chen2, Feng Wang2
1Department of Pediatrics, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.
Insights
Researchers identified three key genes (CD163, MCEMP1, RETN) linked to fatal pediatric septic shock. This discovery offers new insights into sepsis mortality mechanisms and potential therapeutic targets for children.
Area of Science:
- Pediatric critical care medicine
- Bioinformatics
- Computational biology
Background:
- Septic shock in children is a life-threatening infectious disease with high mortality.
- Understanding the mechanisms of death in pediatric sepsis is crucial for improving patient outcomes.
- Early prediction of mortality risk aids in clinical decision-making and treatment strategies.
Purpose of the Study:
- To identify key genes and pathways associated with fatal sepsis in children using bioinformatics and machine learning.
- To provide a theoretical basis for targeted therapies, including Traditional Chinese Medicine (TCM).
- To uncover novel genetic markers for predicting sepsis-related death in pediatric patients.
Main Methods:
- Analysis of gene expression profiles from the GEO database (GSE4607) comparing non-fatal and fatal pediatric sepsis cases.
- Identification of differentially expressed genes (DEGs) and enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
- Construction of protein-protein interaction (PPI) networks and application of machine learning algorithms (LASSO, Random Forest, SVM-RFE) to identify core diagnostic genes.
Main Results:
- 83 differentially expressed genes were identified, with 78 upregulated and 5 downregulated.
- Protein-protein interaction network analysis highlighted 17 candidate genes.
- Three core genes—CD163, MCEMP1, and RETN—were identified as having diagnostic value and potentially regulating pathways like complement and coagulation cascades.
Conclusions:
- CD163, MCEMP1, and RETN were identified as key genes associated with sepsis-related mortality in children.
- These genes may jointly influence critical biological pathways involved in sepsis pathogenesis.
- The findings offer a novel understanding of pediatric sepsis lethality and suggest potential therapeutic targets.
Background:
Septic 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.
Methods:
Gene 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.
Results:
Analysis 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.
Conclusion:
In 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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