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Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Pediatric Sepsis
Insights
This study identifies key genes and microRNAs involved in pediatric sepsis, offering potential biomarkers for improved diagnosis and novel therapeutic strategies in children. These findings aim to enhance clinical sepsis treatments.
Area of Science:
- Genomics and Bioinformatics
- Pediatric Infectious Diseases
- Molecular Biology
Background:
- Sepsis presents a significant health challenge in children, characterized by high mortality rates.
- The underlying pathogenic mechanisms of pediatric sepsis remain incompletely understood.
- There is a critical need for enhanced insights into pediatric sepsis for effective clinical management.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in pediatric sepsis through comprehensive genomic analysis.
- To provide novel insights into potential therapeutic targets for pediatric sepsis.
- To explore molecular mechanisms contributing to sepsis pathogenesis in children.
Main Methods:
- Utilized three pediatric gene expression datasets (GSE25504, GSE26378, GSE26440) from the Gene Expression Omnibus (GEO) database.
- Employed GEO2R for DEG screening, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
- Identified hub genes using Cytoscape and CytoHubba, and constructed targeted microRNA (miRNA) networks with NetworkAnalyst.
Main Results:
- Identified 160 upregulated and 61 downregulated overlapping genes in pediatric sepsis.
- Enriched pathways included hematopoietic cell lineage, Staphylococcus aureus infection, and tumor necrosis factor (TNF) signaling.
- Selected 9 hub genes (e.g., ITGAM, TLR8, IL1ß) and 5 key miRNAs (e.g., has-miR-204-5p, has-miR-21-5p) potentially crucial in pediatric sepsis.
Conclusions:
- The identified DEGs and hub genes offer potential biomarkers for pediatric sepsis.
- Predicted key miRNAs may represent novel therapeutic targets for sepsis treatment in children.
- Findings contribute to developing innovative strategies for managing pediatric sepsis.
Abstract:
BACKGROUND Sepsis is an extremely common health issue with a considerable mortality rate in children. Our understanding about the pathogenic mechanisms of sepsis is limited. The aim of this study was to identify the differential expression genes (DEGs) in pediatric sepsis through comprehensive analysis, and to provide specific insights for the clinical sepsis therapies in children. MATERIAL AND METHODS Three pediatric gene expression profiles (GSE25504, GSE26378, GSE26440) were downloaded from the Gene Expression Omnibus (GEO) database. The difference expression genes (DEGs) between pediatric sepsis and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. RESULTS Totally, 160 overlapping upward genes and 61 downward genes were identified. In addition, 5 KEGG pathways, including hematopoietic cell lineage, Staphylococcus aureus infection, starch and sucrose metabolism, osteoclast differentiation, and tumor necrosis factor (TNF) signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the protein-protein interaction (PPI) network and CytoHubba, 9 hub genes including ITGAM, TLR8, IL1ß, MMP9, MPO, FPR2, ELANE, SPI1, and C3AR1 were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including has-miR-204-5p, has-miR-211-5p, has-miR-590-5p, and has-miR-21-5p, were predicted as possibly the key miRNAs. CONCLUSIONS Our findings will contribute to identification of potential biomarkers and novel strategies for pediatric sepsis treatment.
