Efficacy of Integrating a Novel 16-Gene Biomarker Panel and Intelligence Classifiers for Differential Diagnosis of Rheumatoid Arthritis and Osteoarthritis.

Long NP1, Park S2, Anh NH3, Min JE4, Yoon SJ5, Kim HM6, Nghi TD7, Lim DK8, Park JH9, Lim J10, Kwon SW11.

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Abstract

Introducing novel biomarkers for accurately detecting and differentiating rheumatoid arthritis (RA) and osteoarthritis (OA) using clinical samples is essential. In the current study, we searched for a novel data-driven gene signature of synovial tissues to differentiate RA from OA patients. Fifty-three RA, 41 OA, and 25 normal microarray-based transcriptome samples were utilized. The area under the curve random forests (RF) variable importance measurement was applied to seek the most influential differential genes between RA and OA. Five algorithms including RF, k-nearest neighbors (kNN), support vector machines (SVM), naïve-Bayes, and a tree-based method were employed for the classification. We found a 16-gene signature that could effectively differentiate RA from OA, including TMOD1, POP7, SGCA, KLRD1, ALOX5, RAB22A, ANK3, PTPN3, GZMK, CLU, GZMB, FBXL7, TNFRSF4, IL32, MXRA7, and CD8A. The externally validated accuracy of the RF model was 0.96 (sensitivity = 1.00, specificity = 0.90). Likewise, the accuracy of kNN, SVM, naïve-Bayes, and decision tree was 0.96, 0.96, 0.96, and 0.91, respectively. Functional meta-analysis exhibited the differential pathological processes of RA and OA; suggested promising targets for further mechanistic and therapeutic studies. In conclusion, the proposed genetic signature combined with sophisticated classification methods may improve the diagnosis and management of RA patients.