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Isolating Human Peripheral Blood Mononuclear Cells and CD4+ T cells from Sézary Syndrome Patients for Transcriptomic Profiling
Published on: October 14, 2021
Multi-cohort transcriptomics integration for building and validating a diagnostic model of peripheral blood septic
Ling Li1, Kexun Li1, Weiwei Qian2,3
1Emergency Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Frontiers in Immunology
|June 10, 2026
Summary
This study identifies five neutrophil genes as a diagnostic signature for septic shock, utilizing an artificial neural network (ANN) model. The METTL14/YTHDF1-mediated m6A-S100A12 axis in neutrophils is revealed as a potential therapeutic target.
Area of Science:
- Genomics and Molecular Biology
- Immunology
- Systems Biology
Background:
- Septic shock diagnosis relies on clinical parameters, often leading to delayed treatment.
- Molecular biomarkers are needed for early and accurate septic shock detection.
- Understanding gene regulation in sepsis is crucial for developing targeted therapies.
Purpose of the Study:
- To identify diagnostic signature genes for septic shock from multi-cohort transcriptomic data.
- To establish a peripheral blood molecular diagnostic model for septic shock.
- To elucidate the m6A regulatory mechanisms of key genes in septic shock.
Main Methods:
- Differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) across five peripheral blood cohorts.
- Machine learning algorithms (LASSO, SVM-RFE, random forest) and Protein-Protein Interaction (PPI) networks for feature gene selection.
- Construction and validation of a 5-gene artificial neural network (ANN) diagnostic model; analysis of immune cell composition and gene expression in neutrophils using CIBERSORT and single-cell data; elucidation of the m6A regulatory axis via molecular experiments and in vivo mouse models.
Main Results:
- A diagnostic signature of five genes (S100A12, MMP8, PGLYRP1, CEACAM8, MMP9) was identified, enriched in neutrophil-associated bacterial defense pathways.
- The ANN model demonstrated high diagnostic accuracy across multiple cohorts, with elevated gene expression in clinical sepsis patients.
- Significant neutrophil expansion was observed, with the five signature genes predominantly expressed in neutrophils and correlating with disease severity.
- The METTL14/YTHDF1-mediated m6A modification pathway was shown to stabilize S100A12 mRNA, and its in vivo silencing reduced lung injury in mice.
Conclusions:
- A robust 5-gene diagnostic signature and ANN model for septic shock were established, highlighting neutrophil involvement.
- The METTL14/YTHDF1-mediated m6A-S100A12 axis in neutrophils plays a critical role in septic shock pathogenesis.
- The METTL14/m6A pathway presents a promising target for septic shock diagnosis and therapy.
