{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:37:34Z","timestamp":1787225854646,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":227,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008750","name":"Shanghai Municipal Hospital Development Center","doi-asserted-by":"publisher","award":["SHDC12018106"],"award-info":[{"award-number":["SHDC12018106"]}],"id":[{"id":"10.13039\/501100008750","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["20152214"],"award-info":[{"award-number":["20152214"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974251"],"award-info":[{"award-number":["81974251"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Systemic juvenile idiopathic arthritis (sJIA) is a severe autoinflammatory disorder with a still not clearly defined molecular mechanism. To better understand the disease, we used scattered datasets from public domains and performed a weighted gene coexpression network analysis (WGCNA) to identify key modules and hub genes underlying sJIA pathogenesis. Two gene expression datasets, GSE7753 and GSE13501, were used to construct the WGCNA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to the genes and hub genes in the sJIA modules. Cytoscape was used to screen and visualize the hub genes. We further compared the hub genes with the genome\u2010wide association study (GWAS) genes and used a consensus WGCNA to verify that our conclusions were conservative and reproducible across multiple independent datasets. A total of 5,414 genes were obtained for WGCNA, from which highly correlated genes were divided into 17 modules. The red module demonstrated the highest correlation with the sJIA module (<jats:italic>r<\/jats:italic> = 0.8, <jats:italic>p<\/jats:italic> = 3<jats:italic>e<\/jats:italic><jats:sup>\u221229<\/jats:sup>), whereas the green\u2010yellow module was found to be closely related to the non\u2010sJIA module (<jats:italic>r<\/jats:italic> = 0.62, <jats:italic>p<\/jats:italic> = 1<jats:italic>e<\/jats:italic><jats:sup>\u221214<\/jats:sup>). Functional enrichment analysis demonstrated that the red module was mostly enriched in the activation of immune responses, infection, nucleosomes, and erythrocytes, and the green\u2010yellow module was mostly enriched in immune responses and inflammation. Additionally, the hub genes in the red module were highly enriched in erythrocyte differentiation, including <jats:italic>ALAS2<\/jats:italic>, <jats:italic>AHSP<\/jats:italic>, <jats:italic>TRIM10<\/jats:italic>, <jats:italic>TRIM58<\/jats:italic>, and <jats:italic>KLF1<\/jats:italic>. The hub genes from the green\u2010yellow module were mainly associated with immune responses, as exemplified by the genes KLRB1, KLRF1, CD160, and KIRs. We identified sJIA\u2010related modules and several hub genes that might be associated with the development of sJIA. Particularly, the modules may help understand the mechanisms of sJIA, and the hub genes may become biomarkers and therapeutic targets of sJIA in the future.<\/jats:p>","DOI":"10.1155\/2021\/9957569","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T21:50:34Z","timestamp":1629150634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Application of Weighted Gene Coexpression Network Analysis to Identify Key Modules and Hub Genes in Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6183-738X","authenticated-orcid":false,"given":"Mi","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0066-9153","authenticated-orcid":false,"given":"Ruru","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-6291","authenticated-orcid":false,"given":"Yong-Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0063-6327","authenticated-orcid":false,"given":"Wanling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7491-0854","authenticated-orcid":false,"given":"Rongxiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-4751","authenticated-orcid":false,"given":"Liangjing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"e_1_2_12_1_2","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty R. 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