{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T21:02:35Z","timestamp":1785531755989,"version":"3.56.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Guang dong Medical Research Fund Project","award":["A2024728"],"award-info":[{"award-number":["A2024728"]}]},{"name":"Guang dong Medical Research Fund Project","award":["A2024723"],"award-info":[{"award-number":["A2024723"]}]},{"name":"Zhanjiang Science and Technology Research Project in 2024","award":["2024B01356"],"award-info":[{"award-number":["2024B01356"]}]},{"name":"the High-level Talents Scientific Research Start-up Funds of the Affiliated Hospital of Guangdong Medical University","award":["GCC2022028"],"award-info":[{"award-number":["GCC2022028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Our study aims to explore the early genomic diagnostic markers of OSA and the corresponding drug prediction targets using network pharmacology analysis, and to elucidate the etiology and pathogenesis of OSA from the genetic level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We selected OSA-related gene datasets (GSE135917 and GSE38792) from the Gene Expression Omnibus (GEO). Principal component analysis (PCA) was performed to remove outlier samples, and batch correction was applied to the two datasets. The raw expression matrix was log2-transformed, and samples were divided into normal and OSA groups. Differentially expressed genes (DEGs) were identified, and WGCNA analysis was performed on these DEGs to identify mitochondria-associated hub genes, followed by functional enrichment analysis, PPI network construction, core lncRNA-related ceRNA network construction. We then screened core genes with a high risk of OSA. Based on the core genes, we established an easy-to-use nomogram and verified its accuracy in identifying OSA patients then performed a differential expression analysis of the core genes, GSEA and GSVA analyses, and immune infiltration analysis. Finally, we constructed the disease prediction model and predicted the drug targets, thereby obtain a genomic prediction model for OSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After PCA and batch correction, an expression matrix comprising 13 normal samples and 19 OSA patient samples was finally included. We identified 1500 differentially expressed genes (DEGs) through differential expression analysis, then screened 61 hub genes by WGCNA analysis, and established an OSA-associated ceRNA network containing 75 predictive miRNAs, 129 lncRNAs and 5 mRNAs. Six robust key genes were identified through PPI network construction: TUFM, CYCS, UQCRC1, COX4I1, TIMM50, and NDUFV1. Finally, after LASSO regression and nomogram validation, a predictive model containing 2 core genes (UQCRC1 and COX4I1) was obtained, and its area under the ROC curve (AUC) was 0.919. Drug target prediction of the core genes showed that 1-Methyl-4-phenyl-2,3-dihydropyridinium CTD 00002003, Cube root extract CTD 00006707, Disodium selenite CTD 00007229, and mitotane CTD 00006344 had good effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our current findings provide a rationale for identifying therapeutic targets in the diagnosis and treatment of OSA. In addition, these findings have the potential to facilitate the translation of our study to clinical applications in the future.<\/jats:p>\n                    <jats:p>Insight Box Different from other single-gene predictors of OSA, network pharmacological analysis identified differential genes and explored biomolecular markers of OSA from multi-gene and multi-target perspectives through enrichment analysis, construction of ceRNA gene network, and correlation analysis and explore early genomic diagnostic indicators of OSA and corresponding drug prediction targets using network pharmacological analysis and to elucidate the etiology and pathogenesis of OSA from the genetic level. To provide a more accurate method for the diagnosis, prevention, and treatment of clinical OSA, it is expected to provide a research basis for the accurate diagnosis of clinical OSA and the pathogenesis of OSA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/intbio\/zyag013","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:52:54Z","timestamp":1784807574000},"source":"Crossref","is-referenced-by-count":0,"title":["Potential therapeutic targets for obstructive sleep Apnea were identified through network pharmacology, WGCNA, machine learning, immune infiltration analysis, and ceRNA network"],"prefix":"10.1093","volume":"18","author":[{"given":"Fengwei","family":"Xie","sequence":"first","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3747-6308","authenticated-orcid":false,"given":"Dikun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitong","family":"Yang","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xian","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7525-6615","authenticated-orcid":false,"given":"Dingyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyin","family":"Lin","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyue","family":"Song","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Liu","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4761-4263","authenticated-orcid":false,"given":"Tianhuang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingpin","family":"Pang","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xishi","family":"Sun","sequence":"additional","affiliation":[{"name":"Emergency Medicine Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang 524023, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2026073115025231800_ref1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19095473","article-title":"OSA and chronic respiratory disease: mechanisms and epidemiology","volume":"19","author":"Locke","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"2026073115025231800_ref2","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/S0140-6736(13)60734-5","article-title":"Adult obstructive sleep apnoea","volume":"383","author":"Jordan","year":"2014","journal-title":"The Lancet"},{"key":"2026073115025231800_ref3","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1164\/rccm.202109-2044OC","article-title":"Genome-wide association study of obstructive sleep Apnea and objective sleep-related traits identifies novel risk loci in Han Chinese individuals","volume":"206","author":"Xu","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"2026073115025231800_ref4","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041061","article-title":"Potential pathophysiological pathways in the complex relationships between OSA and cancer","volume":"15","author":"S\u00e1nchez-de-la-Torre","year":"2023","journal-title":"Cancers (Basel)"},{"key":"2026073115025231800_ref5","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/S2213-2600(15)00043-0","article-title":"Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study","volume":"3","author":"Heinzer","year":"2015","journal-title":"Lancet Respir Med"},{"key":"2026073115025231800_ref6","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s11325-012-0785-0","article-title":"High prevalence of undiagnosed obstructive sleep apnoea in the general population and methods for screening for representative controls","volume":"17","author":"Simpson","year":"2013","journal-title":"Sleep Breath"},{"key":"2026073115025231800_ref7","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1007\/s11739-022-02983-1","article-title":"Treatment options in obstructive sleep apnea","volume":"17","author":"Gambino","year":"2022","journal-title":"Intern Emerg Med"},{"key":"2026073115025231800_ref8","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsab030","article-title":"Metrics of sleep apnea severity: beyond the apnea-hypopnea index","volume":"44","author":"Malhotra","year":"2021","journal-title":"Sleep"},{"key":"2026073115025231800_ref9","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1164\/rccm.201512-2431OC","article-title":"Genetic associations with obstructive sleep Apnea traits in Hispanic\/Latino Americans","volume":"194","author":"Cade","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026073115025231800_ref10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/3993509","article-title":"Identifying obstructive sleep Apnea syndrome-associated genes and pathways through weighted gene Coexpression network analysis","volume":"2022","author":"Li","year":"2022","journal-title":"Comput Math Methods Med"},{"key":"2026073115025231800_ref11","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.tips.2021.11.004","article-title":"Network pharmacology: curing causal mechanisms instead of treating symptoms","volume":"43","author":"Nogales","year":"2022","journal-title":"Trends Pharmacol Sci"},{"key":"2026073115025231800_ref12","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2026073115025231800_ref13","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1089\/ars.2014.5955","article-title":"Can mitochondrial dysfunction Be a predictive factor for oxidative stress in patients with obstructive sleep Apnea?","volume":"21","author":"Kim","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"2026073115025231800_ref14","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.16608","article-title":"Identification of novel biomarkers in obstructive sleep apnea via integrated bioinformatics analysis and experimental validation","volume":"11","author":"Zhang","year":"2023","journal-title":"PeerJ"},{"key":"2026073115025231800_ref15","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1093\/aje\/kws342","article-title":"Increased prevalence of sleep-disordered breathing in adults","volume":"177","author":"Peppard","year":"2013","journal-title":"Am J Epidemiol"},{"key":"2026073115025231800_ref16","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.chest.2019.09.002","article-title":"Phenotypic subtypes of OSA: a challenge and opportunity for precision medicine","volume":"157","author":"Zinchuk","year":"2020","journal-title":"Chest"},{"key":"2026073115025231800_ref17","doi-asserted-by":"publisher","first-page":"e24435","DOI":"10.1097\/MD.0000000000024435","article-title":"Screening and identification of potential biomarkers for obstructive sleep apnea via microarray analysis","volume":"100","author":"Cao","year":"2021","journal-title":"Medicine"},{"key":"2026073115025231800_ref18","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1002\/mds.28412","article-title":"Impact of obstructive sleep Apnea on cognitive and motor functions in Parkinson's disease","volume":"36","author":"Elfil","year":"2021","journal-title":"Mov Disord"},{"key":"2026073115025231800_ref19","doi-asserted-by":"publisher","first-page":"846","DOI":"10.4254\/wjh.v7.i6.846","article-title":"Non-alcoholic fatty liver disease: the diagnosis and management. World","volume":"7","author":"Abd el-Kader","year":"2015","journal-title":"J Hepatol"},{"key":"2026073115025231800_ref20","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.metabol.2016.05.004","article-title":"Nonalcoholic fatty liver disease and obstructive sleep apnea","volume":"65","author":"Aron-Wisnewsky","year":"2016","journal-title":"Metabolism: Clinical and Experimental"},{"key":"2026073115025231800_ref21","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1056\/NEJMra011775","article-title":"Nonalcoholic fatty liver disease","volume":"346","author":"Angulo","year":"2002","journal-title":"N Engl J Med"},{"key":"2026073115025231800_ref22","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing","volume":"292","author":"Ivan","year":"2001","journal-title":"Science"},{"key":"2026073115025231800_ref23","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1161\/ATVBAHA.120.315214","article-title":"Hypoxia-mediated regulation of histone demethylases affects angiogenesis-associated functions in endothelial cells","volume":"40","author":"Liu","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026073115025231800_ref24","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.resp.2010.09.001","article-title":"Reactive oxygen species and the brain in sleep apnea","volume":"174","author":"Wang","year":"2010","journal-title":"Respir Physiol Neurobiol"},{"key":"2026073115025231800_ref25","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1007\/s00018-019-03007-6","article-title":"Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice","volume":"76","author":"Shan","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"2026073115025231800_ref26","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1093\/brain\/awaa279","article-title":"Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy","volume":"143","author":"Lin","year":"2020","journal-title":"Brain"},{"key":"2026073115025231800_ref27","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1002\/ajmg.a.61288","article-title":"Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression, intellectual disability, and seizures","volume":"179","author":"Pillai","year":"2019","journal-title":"Am J Med Genet A"},{"key":"2026073115025231800_ref28","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/ejhg.2017.112","article-title":"Mutation in the COX4I1 gene is associated with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia","volume":"25","author":"Abu-Libdeh","year":"2017","journal-title":"Eur J Hum Genet"},{"key":"2026073115025231800_ref29","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020369","article-title":"Loss of COX4I1 leads to combined respiratory chain deficiency and impaired mitochondrial protein synthesis","volume":"10","author":"\u010cun\u00e1tov\u00e1","year":"2021","journal-title":"Cells"},{"key":"2026073115025231800_ref30","doi-asserted-by":"publisher","first-page":"225","DOI":"10.24920\/003834","article-title":"Adiponectin ameliorated pancreatic islet injury induced by chronic intermittent hypoxia through inhibiting the imbalance in mitochondrial fusion and division","volume":"36","author":"He","year":"2021","journal-title":"Chin Med Sci J"},{"key":"2026073115025231800_ref31","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41392-023-01496-3","article-title":"Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome","volume":"8","author":"Lv","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"2026073115025231800_ref32","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1113\/JP273312","article-title":"Adipose tissue inflammation by intermittent hypoxia: mechanistic link between obstructive sleep apnoea and metabolic dysfunction","volume":"595","author":"Ryan","year":"2017","journal-title":"J Physiol"},{"key":"2026073115025231800_ref33","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1056691","article-title":"Construction of a mitochondrial dysfunction related signature of diagnosed model to obstructive sleep apnea","volume":"13","author":"Liu","year":"2022","journal-title":"Front Genet"},{"key":"2026073115025231800_ref34","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13091080","article-title":"Impaired upper airway muscle function with excessive or deficient dietary intake of selenium in rats","volume":"13","author":"Burns","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"2026073115025231800_ref35","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1530\/ERC-12-0368","article-title":"Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells","volume":"20","author":"Hescot","year":"2013","journal-title":"Endocr Relat Cancer"}],"container-title":["Integrative Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ib\/article-pdf\/doi\/10.1093\/intbio\/zyag013\/70416773\/zyag013.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ib\/article-pdf\/doi\/10.1093\/intbio\/zyag013\/70416773\/zyag013.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:02:58Z","timestamp":1785524578000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ib\/article\/doi\/10.1093\/intbio\/zyag013\/8748604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":35,"URL":"https:\/\/doi.org\/10.1093\/intbio\/zyag013","relation":{},"ISSN":["1757-9708"],"issn-type":[{"value":"1757-9708","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2026,1]]},"article-number":"zyag013"}}