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Updated: Jun 12, 2025
A Data-Driven Approach to Quantifying Immune States in Sepsis
Published on: February 7, 2025
Data-driven analysis that integrates bioinformatics and machine learning uncovers PANoptosis-related diagnostic genes
Jing Wang1, ShiFeng Chen1, Lei Chen1
1Department of Clinical Laboratory Center, Yantai Yuhuangding Hospital, Yantai, 264099, Shandong, China.
Insights
This study identifies five PANoptosis genes (ANXA3, S100A9, TXN, CLEC5A, TMEM263) as key biomarkers for the early detection of pediatric septic shock, improving diagnostic accuracy and understanding disease mechanisms.
Area of Science:
- Immunology
- Pediatric Critical Care
- Genomics
Background:
- Sepsis is a leading cause of mortality in children globally, with refractory septic shock posing a significant threat.
- PANoptosis, a unique inflammatory cell death mechanism resulting from pyroptosis, apoptosis, and necroptosis interactions, is implicated in various conditions including infections.
Purpose of the Study:
- To enhance the diagnostic capability of PANoptosis-related gene signatures for early identification of pediatric septic shock.
- To identify a robust set of genes indicative of PANoptosis in pediatric septic shock.
Main Methods:
- Analysis of differentially expressed genes (DEGs) in pediatric septic shock cohorts (GSE66099).
- Weighted gene co-expression network analysis (WCGNA) to identify key gene modules.
- Random forest and LASSO regression for selecting PANoptosis diagnostic signature genes.
- Validation of signature genes across four independent cohorts (GSE26378, GSE26440, GSE8121, GSE13904).
Main Results:
- The MEgrey module significantly correlated with pediatric septic shock (p < 0.0001).
- Five PANoptosis-related signature genes were identified: ANXA3, S100A9, TXN, CLEC5A, and TMEM263.
- The diagnostic efficacy of these genes was confirmed with high Area Under the Curve (AUC) values in validation cohorts, reaching up to 0.994.
Conclusions:
- The identified PANoptosis genes (ANXA3, S100A9, TXN, CLEC5A, TMEM263) are valuable for early detection of pediatric septic shock.
- These findings contribute to understanding immune cell infiltration in pediatric septic shock pathophysiology.
- Further basic and clinical research is warranted to confirm these early results.
Objectives:
Sepsis is one of the leading causes of death for children worldwide. Additionally, refractory septic shock is one of the most significant groups that contributes to a high death rate. The interaction of pyroptosis, apoptosis, and necroptosis results in a unique inflammatory cell death mechanism known as PANoptosis. An increasing amount of evidence suggests that PANoptosis can be brought on by several stimuli, including cytokine storms, malignancy, and bacterial or viral infections. The goal of this study is to improve the diagnostic significance of the PANoptosis-related gene signature in early pediatric septic shock.
Design And Methods:
We examined children with septic shock from the GSE66099 discovery cohort and looked at differentially expressed genes (DEGs). To filter the important modules, weighted gene co-expression network analysis (WCGNA) was employed. In the end, random forest analysis and the least absolute shrinkage and selection operator (LASSO) were used to determine the PANoptosis diagnostic signature genes. To determine the PANoptosis signature genes, we also found four validation cohorts: GSE26378, GSE26440, GSE8121, and GSE13904. The area under the curve (AUC) of the receiver operating characteristic curves (ROCs), along with sensitivity, specificity, positive predictive value, and negative predictive value, were used to assess the diagnostic efficacy of these signature genes.
Results:
From GSE66099, 1142 DEGs in total were tested. Following the WGCNA clustering of the data into 16 modules, the MEgrey module showed a significant correlation with pediatric septic shock (p < 0.0001). Following the use of LASSO and random forest algorithms to identify the PANoptosis-related signature genes, which include ANXA3, S100A9, TXN, CLEC5A, and TMEM263. These signature genes' receiver operating characteristic curves (ROCs) were confirmed in the external dataset from GSE26378, GSE26440, GSE8121, and GSE13904, and were 0.994 (95 % CI 0.987-0.999), 0.987 (95 % CI 0.974-0.997), 0.957 (95 % CI 0.927-0.981), 0.974 (95 % CI 0.954-0.988), 0.897 (95 % CI 0.846-0.941), respectively.
Conclusion:
In summary, the discovery of PANoptosis genes, ANXA3, S100A9, TXN, CLEC5A, and TMEM263 proved to be quite helpful in the early detection of pediatric septic shock patients. These early results, which need to be further confirmed in basic and clinical research, are extremely important for understanding immune cell infiltration in the pathophysiology of pediatric septic shock.
