{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:28:00Z","timestamp":1789043280958,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Nerve injury triggers complex molecular responses involving immune activation and neuronal damage, yet the key regulatory genes and their mechanisms remain poorly understood. Here, we integrated multi\u2010transcriptomic datasets and machine learning to identify and validate novel biomarkers of nerve injury and elucidate their functional roles.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The RNA\u2010seq data and the single\u2010cell transcriptome data of nerve injury and sham\u2010surgery samples were sourced from the Gene Expression Omnibus (GEO) database. Weighted gene co\u2010expression network analysis (WGCNA), differential expression analysis, and three machine learning algorithms were used to identify hub genes associated with nerve injury. The expression patterns and diagnostic value of these hub genes were validated in independent datasets. The correlation between these genes and immune cell infiltration was analyzed using the CIBERSORT algorithm. Finally, single\u2010cell RNA sequencing (scRNA\u2010seq) data were used to investigate the cell\u2010specific expression patterns of the hub genes in neural cells.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Seven nerve injury\u2010related genes were identified via WGCNA and three machine learning methods, of which\n Atf3<\/jats:italic>\n ,\n Bin2<\/jats:italic>\n ,\n Fcgr2b<\/jats:italic>\n , and\n Ucn<\/jats:italic>\n exhibited robust diagnostic performance (AUC > 0.7) across validation cohorts. Functional enrichment implicated these genes in neuroinflammation, neuronal fate commitment, and JAK\u2010STAT\/NF\u2010\u03baB signaling. Immune infiltration analysis correlated their expression with M2 macrophage polarization and CD4+ T cell depletion, while scRNA\u2010seq highlighted cell\u2010specific patterns:\n Atf3<\/jats:italic>\n and\n Ucn<\/jats:italic>\n were neuron\u2010enriched, whereas\n Fcgr2b<\/jats:italic>\n and\n Bin2<\/jats:italic>\n predominated in macrophages\/NK cells. Moreover,\n Fcgr2b<\/jats:italic>\n promoted the outgrowth of neurites in PC12 cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our study unveils\n Atf3<\/jats:italic>\n ,\n Bin2<\/jats:italic>\n ,\n Fcgr2b<\/jats:italic>\n , and\n Ucn<\/jats:italic>\n as critical nerve injury biomarkers with dual roles in neuroimmune crosstalk, offering novel insights into therapeutic targeting for nerve repair. Moreover,\n Fcgr2b<\/jats:italic>\n may be involved in neurite outgrowth after nerve injury.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/brb3.71279","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:31:58Z","timestamp":1772965918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Screening Biomarkers for Nerve Injury Using Weighted Gene Co\u2010Expression Network Analysis and Machine Learning"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9986-6754","authenticated-orcid":false,"given":"Shuming","family":"Cao","sequence":"first","affiliation":[{"name":"Clinical School\/College of Orthopedics Tianjin Medical University Tianjin China"},{"name":"Department of Hand Surgery Tianjin Hospital Tianjin 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