Evidence mapPaperPMID 42266692Full record

ArticleFrontiers in immunology2026

Multi-cohort transcriptomics integration for building and validating a diagnostic model of peripheral blood septic shock.

Ling Li, Kexun Li, Weiwei Qian, Hui Jiang, Hongqiong Peng, Yang Zhang, Zhengjun Chen, Xia Zeng

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Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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8 authors.

Ling Li *Emergency Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Kexun Li *Emergency Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Weiwei Qian *Emergency Department, Shangjinnanfu Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Hui JiangEmergency Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Hongqiong PengEmergency Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Yang ZhangEmergency Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Zhengjun ChenRobotic Minimally Invasive Surgery Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Xia ZengEmergency Department, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: To integrate multi-cohort transcriptomic, single-cell, and experimental data to identify diagnostic signature genes for septic shock, establish a peripheral blood molecular diagnostic model, and elucidate the m6A regulatory mechanisms of key genes. Methods: Candidate genes were identified from five GEO peripheral blood cohorts through batch effect-corrected differential expression analysis and WGCNA, followed by parallel GO/DO enrichment analysis. Feature genes were selected using PPI networks combined with LASSO, SVM-RFE, and random forest algorithms. A 5-gene artificial neural network (ANN) diagnostic model was constructed and validated using ROC and logistic regression in GSE95233, GSE131761, and clinical cohorts. Immune cell composition and expression of characteristic genes in neutrophils were analyzed using CIBERSORT and GSE167363 single-cell data. The METTL14/YTHDF1-S100A12 m6A axis was elucidated via qRT-PCR, Western blot, MeRIP-qPCR, RIP-qPCR, and Actinomycin D experiments. In CLP mice, siMETTL14 was administered for Results: A total of 76 sepsis-shock-associated candidate genes were identified, enriched in the bacterial defense pathway. Five robust candidate genes (S100A12, MMP8, PGLYRP1, CEACAM8, MMP9) were selected by integrating PPI and three machine learning algorithms. The constructed ANN achieved high AUC across multiple cohorts, and all five genes showed significantly elevated mRNA and protein levels in peripheral blood from clinical sepsis patients. CIBERSORT and single-cell results indicated significant neutrophil expansion, with the five genes predominantly enriched in neutrophils and progressively elevated with worsening outcomes. m6A-related experiments demonstrated that METTL14 mediates m6A modification and stabilizes S100A12 mRNA through YTHDF1 recognition; knocking down either METTL14 or YTHDF1 accelerated its degradation. Conclusion: In this study, a diagnostic signature was established for septic shock comprising five neutrophil-associated genes and an ANN model, revealing the regulatory role of the METTL14/YTHDF1-mediated m6A-S100A12 axis in neutrophils. This suggests the METTL14/m6A pathway as a potential diagnostic and therapeutic target.

Indexed as

Shock, SepticTranscriptomeAnimalsBiomarkersCohort StudiesDisease Models, AnimalGene Expression ProfilingHumansMiceNeutrophilsBiomarkersartificial neural networkdiagnostic gene signaturem6a modificationperipheral blood transcriptomeseptic shock

Identifiers

PMID42266692
PMCPMC13243033

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.