{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:43:33Z","timestamp":1769694213575,"version":"3.49.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>The coronavirus disease 2019 (COVID-19), emerged in late 2019, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The risk factors for idiopathic pulmonary fibrosis (IPF) and COVID-19 are reported to be common. This study aimed to determine the potential role of differentially expressed genes (DEGs) common in IPF and COVID-19.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>Based on GEO database, we obtained DEGs from one SARS-CoV-2 dataset and five IPF datasets. A series of enrichment analysis were performed to identify the function of upregulated and downregulated DEGs, respectively. Two plugins in Cytoscape, Cytohubba and MCODE, were utilized to identify hub genes after a protein-protein interaction (PPI) network. Finally, candidate drugs were predicted to target the upregulated DEGs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 188 DEGs were found between COVID-19 and IPF, out of which 117 were upregulated and 71 were downregulated. The upregulated DEGs were involved in cytokine function, while downregulated DEGs were associated with extracellular matrix disassembly. Twenty-two hub genes were upregulated in COVID-19 and IPF, for which 155 candidate drugs were predicted (adj.P.value &lt; 0.01).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Identifying the hub genes aberrantly regulated in both COVID-19 and IPF may enable development of molecules, encoded by those genes, as therapeutic targets for preventing IPF progression and SARS-CoV-2 infections.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0262737","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T18:33:38Z","timestamp":1642617218000},"page":"e0262737","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of hub genes associated with COVID-19 and idiopathic pulmonary fibrosis by integrated bioinformatics 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Cecchini","year":"2018","journal-title":"Respir Res"},{"issue":"1","key":"pone.0262737.ref011","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12881-017-0449-9","article-title":"Gene expression profiling of idiopathic interstitial pneumonias (IIPs): identification of potential diagnostic markers and therapeutic targets.","volume":"18","author":"Y Horimasu","year":"2017","journal-title":"BMC Med Genet"},{"issue":"1","key":"pone.0262737.ref012","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1136\/thoraxjnl-2013-204596","article-title":"Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis","volume":"70","author":"DJ DePianto","year":"2015","journal-title":"Thorax"},{"key":"pone.0262737.ref013","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1755-8794-4-70","article-title":"Bayesian probit regression model for the diagnosis of pulmonary fibrosis: 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Richeldi","year":"2017","journal-title":"Lancet"},{"issue":"9807","key":"pone.0262737.ref026","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(11)60052-4","article-title":"Idiopathic pulmonary fibrosis","volume":"378","author":"TE King","year":"2011","journal-title":"Lancet"},{"issue":"1","key":"pone.0262737.ref027","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1164\/rccm.202004-1132OC","article-title":"Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. 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