{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:04:23Z","timestamp":1790186663182,"version":"4.1.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Xinjiang Uygur Autonomous Region Natural Science Foundation","award":["2023D01C116"],"award-info":[{"award-number":["2023D01C116"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Periodontitis (PD) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases with potential clinical links, yet their shared molecular mechanisms remain unclear\u2014patients with JIA face elevated periodontal risk, the temporomandibular joint affected in JIA shares inflammatory pathways with PD, Th17 cells drive both conditions, and glucocorticoid therapy may exacerbate periodontal vulnerability. This study aimed to explore the shared mechanisms and potential therapeutic targets of PD and sJIA using genetic expression data from the GEO database and performed comprehensive bioinformatics analyses, including differential expression gene analysis, weighted gene co\u2011expression network analysis (WGCNA), functional enrichment analysis, protein\u2011protein interaction network construction, and machine learning across 175 predictive models with the Ridge\u2009+\u2009AdaBoost ensemble identified as the best\u2011performing combination, followed by SHapley Additive exPlanations (SHAP) for model interpretability, CIBERSORT for immune infiltration assessment, and molecular docking with 100\u2011ns molecular dynamics simulations for therapeutic target validation. We identified 37 shared candidate genes between PD and sJIA, which were significantly enriched in IL\u201117, NF\u2011\u03baB, rheumatoid arthritis, and lipid atherosclerosis pathways, and machine learning screening further selected six core diagnostic genes (\n                    <jats:italic>FAM46C<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL1<\/jats:italic>\n                    ,\n                    <jats:italic>SELP<\/jats:italic>\n                    ,\n                    <jats:italic>LGALSL<\/jats:italic>\n                    ,\n                    <jats:italic>ELOVL4<\/jats:italic>\n                    ,\n                    <jats:italic>VCAN<\/jats:italic>\n                    ), with\n                    <jats:italic>SELP<\/jats:italic>\n                    demonstrating the most robust cross\u2011model, cross\u2011dataset diagnostic value (AUC\u2009&gt;\u20090.8); SHAP analysis confirmed\n                    <jats:italic>SELP<\/jats:italic>\n                    as a stable risk\u2011driving predictor across all models, while\n                    <jats:italic>CXCL1<\/jats:italic>\n                    consistently showed protective effects. Immune infiltration revealed shared neutrophil elevation and CD8\u2009\u207a\u2009T\u2011cell reduction, with conserved\n                    <jats:italic>CXCL1<\/jats:italic>\n                    and\n                    <jats:italic>SELP<\/jats:italic>\n                    correlations with neutrophils and resting mast cells, and\n                    <jats:italic>FAM46C<\/jats:italic>\n                    with plasma cells.Drug\u2011target network analysis identified\n                    <jats:italic>IL1B, MMP<\/jats:italic>\n                    1, and\n                    <jats:italic>ITGAM<\/jats:italic>\n                    as core targets, and molecular docking yielded strong binding affinities for deoxycholic acid\u2013\n                    <jats:italic>MMP1<\/jats:italic>\n                    (\u22127.6 kcal\/mol), kaempferol\u2013\n                    <jats:italic>IL1B<\/jats:italic>\n                    (\u22127.2 kcal\/mol), kaempferol\u2013\n                    <jats:italic>ITGAM<\/jats:italic>\n                    (\u22126.9 kcal\/mol), with MD simulations confirming stable and specific binding. Collectively, this study explores shared genetic and immunological characteristics between PD and sJIA, suggests that\n                    <jats:italic>SELP<\/jats:italic>\n                    may serve as a critical cross\u2011disease diagnostic biomarker, and offers novel insights into their pathogenesis and potential therapeutic targets that warrant further experimental validation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1014669","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:26:28Z","timestamp":1790184388000},"page":"e1014669","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shared pathogenic genes and therapeutic targets in periodontitis and systemic juvenile idiopathic arthritis: An integrative bioinformatics and machine learning study"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2093-1105","authenticated-orcid":true,"given":"Qingao","family":"Deng","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9488-297X","authenticated-orcid":true,"given":"Lu","family":"Qi","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"issue":"6","key":"pcbi.1014669.ref001","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/idj.12630","article-title":"Current Concepts in the Management of Periodontitis","volume":"71","author":"T Kwon","year":"2021","journal-title":"Int Dent J"},{"issue":"7","key":"pcbi.1014669.ref002","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nrmicro2337","article-title":"Periodontitis: a polymicrobial disruption of host homeostasis","volume":"8","author":"RP Darveau","year":"2010","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"pcbi.1014669.ref003","first-page":"235","article-title":"Pathogenesis of inflammatory periodontal disease. 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Batool","year":"2023","journal-title":"Medicine (Baltimore)"},{"issue":"11","key":"pcbi.1014669.ref046","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.molmed.2015.09.001","article-title":"Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders","volume":"21","author":"S Fiorucci","year":"2015","journal-title":"Trends in Molecular Medicine"},{"key":"pcbi.1014669.ref047","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.3389\/fimmu.2017.01866","article-title":"\u03b22 integrins as regulators of dendritic cell, monocyte, and macrophage function","volume":"8","author":"L Schittenhelm","year":"2017","journal-title":"Front Immunol"},{"key":"pcbi.1014669.ref048","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cancergen.2025.04.004","article-title":"Clinicopathological correlation of PTPN3 expression in breast cancer and in silico drug screening against PTPN3 for therapeutics","author":"S Thankachan","year":"2025","journal-title":"Cancer Genet"},{"issue":"1","key":"pcbi.1014669.ref049","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev-biochem-030222-120000","article-title":"The Art and Science of Molecular Docking","volume":"93","author":"JM Paggi","year":"2024","journal-title":"Annu Rev Biochem"},{"key":"pcbi.1014669.ref050","first-page":"1005","article-title":"Demonstrating the absence of correlation between molecular docking and in vitro cytotoxicity in anti-breast cancer research: root causes and practical resolutions","volume":"17","author":"S Megantara","year":"2025","journal-title":"Breast Cancer"},{"key":"pcbi.1014669.ref051","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"P Langfelder","year":"2008","journal-title":"BMC 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