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

Wei Guo^1*Hao Chen²Feng Wang²Yingjiao Chi³Wei Zhang¹Shan Wang⁴Kezhu Chen⁵Hong Chen^1*

• ¹First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
• ²Heilongjiang Provincial Hospital of Traditional Chinese Medicine, Harbin, China
• ³Harbin First Hospital, Harbin, Heilongjiang Province, China
• ⁴Ning 'an Hospital of Traditional Chinese Medicine pediatrics, Ning 'an, China
• ⁵Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China

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 upregulated 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.