{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:31:14Z","timestamp":1773426674129,"version":"3.50.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis is a life-threatening condition caused by a dysregulated immune response, often leading to organ failure and death. Diagnosis and therapy remain challenging. This study aimed to identify biomarkers for sepsis through multi-omics analysis and experimental validation. A total of 1,166 samples from the GEO repository underwent differential analysis, WGCNA, and logistic regression to identify sepsis-associated features. After SVM-RFE screening, a 28-gene signature distinguishing sepsis from healthy controls achieved an AUC of 0.970 (sensitivity 0.939, specificity 1.000) in an independent cohort and 0.870 (sensitivity 0.906, specificity 0.700) in qRT-PCR validation. A 13-gene signature distinguishing sepsis from SIRS achieved an AUC of 1.000 (sensitivity 1.000, specificity 1.000) and 0.745 (sensitivity 0.500, specificity 0.900), respectively. PRKACB, consistently decreased in sepsis, emerged as a myeloid-associated hub gene with functional support in macrophages. Single-cell analysis revealed that PRKACB is predominantly expressed in myeloid cells, with macrophages and neutrophils showing the most notable compositional changes. Pathway enrichment indicated distinct PRKACB-related functions between sepsis and healthy controls, and across myeloid subtypes. Reducing PRKACB expression significantly upregulated TNF-\u03b1 and IL-1\u03b2 release and decreased THP-1 macrophage viability, suggesting that excessive inflammation may trigger apoptosis or metabolic dysfunction. These data support PRKACB as a myeloid hub linked to macrophage inflammatory output and viability, while defining the precise downstream signaling as a priority for future studies.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1611348","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:15:12Z","timestamp":1768454112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-omics machine learning identifies diagnostic gene signatures and functionally supports PRKACB involvement in macrophage inflammatory responses in sepsis"],"prefix":"10.3389","volume":"16","author":[{"given":"Lvying","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Veterans Hospital of Sichuan Province","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sisi","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shangjinnanfu Hospital, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengwen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Laboratory of Emergency Medicine, West China Hospital, and Disaster Medical Center, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cunqiao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shangjinnanfu Hospital, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shangjinnanfu Hospital, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2019-0013","article-title":"INSIGHT MM: a large, global, prospective, non-interventional, real-world study of patients with multiple myeloma","volume":"15","author":"Costello","year":"2019","journal-title":"Future Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1087691","article-title":"Identification of biomarkers related to sepsis diagnosis based on bioinformatics and machine learning and experimental verification","volume":"14","author":"Wang","year":"2023","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/S1473-3099(15)70112-X","article-title":"Sepsis: a roadmap for future research","volume":"15","author":"Cohen","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.87646","article-title":"Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular Traps via GSDMD-N-expressing Mitochondrial Transfer during Sepsis","volume":"20","author":"Kuang","year":"2024","journal-title":"Int J Biol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.84613","article-title":"VDAC2 malonylation participates in sepsis-induced myocardial dysfunction via mitochondrial-related ferroptosis","volume":"19","author":"She","year":"2023","journal-title":"Int J Biol Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/medicina56100527","article-title":"On behalf of the internal medicine sepsis study group. 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