{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:53:51Z","timestamp":1791179631600,"version":"4.1.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rheumatoid Arthritis (RA) is a highly variable and unpredictable autoimmune disease, relying solely on physical symptoms often leads to delayed treatment and irreversible joint destruction. Therefore, identifying biomarkers in RA is necessary to bridge the gap between a patient\u2019s unique biological profile and successful clinical management. This study aims to identify distinct molecular signatures in RA patients by integrating systems biology and case-control methodologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic datasets from various sources specifically synovial tissues, macrophages, blood, T-cells, natural killer T-cells, natural killer cells, neutrophils, and monocytes were analysed. Differentially Expressed Genes and functional enrichment pathways were identified, followed by Weighted Gene Co-expression Network Analysis to pinpoint hub genes. Machine learning models were used to extract consensus biomarkers. Two of the predicted biomarkers IL2RG) and Interferon-Gamma (IFNG) were further validated using an Enzyme-Linked Immunosorbent Assay (ELISA) in RA patient serum samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis revealed that synovial tissues and synovial macrophages exhibited pronounced transcriptomic expression changes. Six consensus biomarkers such as IFNG, PTEN, IL2RG, CDKN2D, VEGFA, and CDKN1A were computationally prioritized in synovial macrophages. Among these, IL2RG and IFNG were selected for preliminary experimental validation by ELISA. IL2RG concentrations were significantly higher in RA patients (1.34 \u00b1 0.11 ng\/mL) than in healthy controls (0.83 \u00b1 0.07 ng\/mL), while IFNG levels showed only a marginal increase (1.91 \u00b1 0.06 pg\/mL) compared to controls (1.69 \u00b1 0.06 pg\/mL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By integrating multi-tissue transcriptomic profiling with machine learning, this study mapped critical molecular changes in RA and prioritized six consensus biomarkers within synovial macrophages. Experimental validation confirmed that IL2RG and IFNG are significantly elevated in RA patients compared to healthy controls. These findings offer a promising, minimally invasive molecular markers for diagnosis and personalized clinical management in RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1891543","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:32:03Z","timestamp":1791178323000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating transcriptomic analysis to explore biomarkers and therapeutic targets for rheumatoid arthritis: a case-control and systems biology approach"],"prefix":"10.3389","volume":"6","author":[{"given":"S.","family":"Aswini","sequence":"first","affiliation":[{"name":"School of Bio Sciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Mohamed Muzammil","sequence":"additional","affiliation":[{"name":"School of Bio Sciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Raja","sequence":"additional","affiliation":[{"name":"Padmavathy Rheumatic Care Centre","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Asha Devi","sequence":"additional","affiliation":[{"name":"School of Bio Sciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"116037","DOI":"10.1016\/j.bcp.2024.116037","article-title":"CXCL13 promotes TNF-\u03b1 synthesis in rheumatoid arthritis through activating ERK\/p38 pathway and inhibiting miR-330-3p generation","volume":"221","author":"Achudhan","year":"2024","journal-title":"Biochem. 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