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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 |
doi: 10.3389/fimmu.2025.1519371
This article is part of the Research Topic Hunting for Inflammation Mediators: Identifying Novel Biomarkers for Autoimmune and Autoinflammatory Diseases View all 3 articles
Identification and Validation of Diagnostic Genes IFI44 and IRF9 in Insomnia-Associated Autoimmune Uveitis
Provisionally accepted- 1 Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- 2 Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
- 3 First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, China
Objective: Insomnia is increasingly recognized as a significant factor in the development of various autoimmune diseases, including autoimmune uveitis (AU). We investigated insomnia-associated genes that may contribute to AU pathogenesis and sought to identify potential biomarkers for insomnia-associated AU.Methods: Microarray data related to insomnia and AU were downloaded from the Gene Expression Omnibus (GEO) database and analyzed. The GEO2R tool was used to identify differentially expressed genes (DEGs) that were common between insomnia and AU. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI), functional enrichment, and CMap analyses were then performed to identify pathogenic genes, underlying mechanisms, and potential therapeutic drugs for insomnia-associated AU. Least absolute shrinkage and selection operator regression was employed to screen for candidate biomarkers, and their diagnostic performance was evaluated using receiver operating characteristic (ROC) curves and quantitative polymerase chain reaction (qPCR). Finally, molecular docking was applied to verify binding activities.We identified 138 up-regulated and 85 down-regulated DEGs that were common to insomnia and AU. PPI network analysis highlighted 10 key genes, CMap analysis identified 30 compounds, and WGCNA revealed 54 key genes and 30 compounds. Intersection of the abovementioned key genes and compounds identified six genes and five compounds. After verification by qPCR and ROC curve analysis, IFI44 and IRF9 were confirmed as hub genes. Finally, two compounds were selected based on docking scores of less than -7 kcal/mol.Our study demonstrated involvement of the viral response in both insomnia and AU and identified the diagnostic significance of IFI44 and IRF9 in these conditions. These findings provide novel insights for future diagnostic and therapeutic strategies to treat insomnia-associated AU.
Keywords: insomnia, Autoimmune uveitis, IFI44, IRF9, CMAP
Received: 29 Oct 2024; Accepted: 14 Jan 2025.
Copyright: © 2025 Wu, Feng, Tian, Chu, Liu, Zeng, Wang, Wang, Hou and LIANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chao Wu, Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
Baorui Chu, Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
Xianyang Liu, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, Chongqing Municipality, China
Shuhao Zeng, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, Chongqing Municipality, China
Yakun Wang, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, Chongqing Municipality, China
Hong Wang, Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
Shengping Hou, Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
QINGFENG LIANG, Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
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