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Updated: Apr 24, 2026
A Data-Driven Approach to Quantifying Immune States in Sepsis
Published on: February 7, 2025
Identification of biomarkers for pediatric sepsis based on machine learning and bioinformatics analysis
Weidong Ye1, Sijia Chen1, You Duan2
1Department of Pediatric, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, China.
Insights
This study identified RORA and GPR183 as key biomarkers for pediatric sepsis, a serious condition. These findings may lead to better diagnostic tools and treatments for children with sepsis.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Genomics
Background:
- Pediatric sepsis presents a significant challenge due to high mortality and lack of effective diagnostic biomarkers.
- Early diagnosis and treatment are hindered by the complex immune dysregulation in pediatric sepsis.
Purpose of the Study:
- To identify novel biomarkers for early diagnosis and potential therapeutic targets in pediatric sepsis.
- To investigate the immune cell infiltration patterns in pediatric sepsis patients.
Main Methods:
- Integrated six bulk RNA-seq datasets (497 patients, 116 controls).
- Utilized weighted gene co-expression network analysis and 14 machine learning models to screen biomarkers.
- Performed functional enrichment and immune infiltration analyses.
- Validated findings in a zebrafish sepsis model.
Main Results:
- Identified 237 high-confidence biomarkers, with RORA and GPR183 showing prominence across multiple models.
- Biomarkers are implicated in transcription, immune response, and cellular senescence.
- Observed reduced adaptive immune cells (B cells, CD8+ T cells) and increased neutrophils/monocytes, suggesting immunoparalysis.
- RORA and GPR183 correlate positively with CD8+ T cells.
- Zebrafish model showed downregulation of rora1, rora2, and gpr183 in sepsis.
Conclusions:
- RORA and GPR183 are promising biomarkers for pediatric sepsis diagnosis and may play a role in T cell regulation.
- Findings offer insights into immune dysregulation in pediatric sepsis and potential therapeutic strategies.
- An open-source website was developed for real-time biomarker application.
Abstract:
Pediatric sepsis is a systemic inflammatory syndrome caused by dysregulated host immune responses, with a high mortality rate and a lack of effective biomarkers, posing significant challenges for early diagnosis and treatment. This study integrated six bulk RNA-seq datasets related to pediatric sepsis, including 497 patients and 116 healthy control samples. Weighted gene co-expression network analysis was used to identify gene modules significantly associated with pediatric sepsis, and 237 high-confidence biomarkers were screened based on 14 machine learning models, among which RORA and GPR183 stood out in multiple models. Functional analysis indicated that these biomarkers were mainly involved in biological processes such as transcription and translation, the immune system, and cellular senescence. Immune infiltration analysis revealed a significant reduction in adaptive immune cells such as B cells and CD8+ T cells and an increase in neutrophil and monocyte infiltration in pediatric sepsis patients, consistent with the "immunoparalysis" theory. Notably, RORA and GPR183 were positively correlated with CD8+ T cells, suggesting their potential role in regulating T cell function. Additionally, we developed an open-source website for real-time application of biomarkers. Furthermore, we established a sepsis model in zebrafish and found that rora1, rora2, and gpr183 expression levels were significantly downregulated in the disease group. This study provides new insights for developing novel diagnostic tools and targeted therapies for pediatric sepsis.
