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Published on: June 18, 2020
Deciphering the molecular classification of pediatric sepsis: integrating WGCNA and machine learning-based
Junming Huang1,2, Jinji Chen2, Chengbang Wang2
1Department of Urology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.
Insights
Pediatric sepsis (PS) involves programmed cell death induced by copper. This study identifies specific cuproptosis-related genes and immune patterns linked to PS, offering new diagnostic insights.
Area of Science:
- Molecular Biology
- Immunology
- Computational Biology
Background:
- Pediatric sepsis (PS) is a critical condition with high mortality.
- The role of copper-induced cell death (cuproptosis) in PS is not well understood.
Purpose of the Study:
- To investigate the involvement of cuproptosis-related genes (CRGs) in pediatric sepsis.
- To analyze the immune landscape associated with PS and cuproptosis.
- To develop a diagnostic model for PS.
Main Methods:
- Analysis of CRG expression and immune landscape in the GSE66099 dataset.
- Consensus clustering of PS samples based on CRGs.
- Weighted gene co-expression network analysis to identify hub genes.
- Application of machine learning for diagnostic model development.
Main Results:
- Aberrant expression of 27 CRGs was observed in PS samples.
- Two distinct cuproptosis clusters with unique immune profiles were identified.
- Extreme Gradient Boosting showed high performance as a PS diagnostic model.
Conclusions:
- Cuproptosis-related genes and immune cell infiltration are implicated in the molecular mechanisms of pediatric sepsis.
- Distinct molecular subtypes of PS based on cuproptosis exist.
- Machine learning models can aid in PS diagnosis.
Abstract:
Introduction: Pediatric sepsis (PS) is a life-threatening infection associated with high mortality rates, necessitating a deeper understanding of its underlying pathological mechanisms. Recently discovered programmed cell death induced by copper has been implicated in various medical conditions, but its potential involvement in PS remains largely unexplored. Methods: We first analyzed the expression patterns of cuproptosis-related genes (CRGs) and assessed the immune landscape of PS using the GSE66099 dataset. Subsequently, PS samples were isolated from the same dataset, and consensus clustering was performed based on differentially expressed CRGs. We applied weighted gene co-expression network analysis to identify hub genes associated with PS and cuproptosis. Results: We observed aberrant expression of 27 CRGs and a specific immune landscape in PS samples. Our findings revealed that patients in the GSE66099 dataset could be categorized into two cuproptosis clusters, each characterized by unique immune landscapes and varying functional classifications or enriched pathways. Among the machine learning approaches, Extreme Gradient Boosting demonstrated optimal performance as a diagnostic model for PS. Discussion: Our study provides valuable insights into the molecular mechanisms underlying PS, highlighting the involvement of cuproptosis-related genes and immune cell infiltration.
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