In RA, the top upstream regulators included IL-12, IL-21, IL-2, SERPINE2 and CD40LG while in SpA the top upstream regulators were: TGFB1, IFNG, MAP3K14, SIRT1 and Alpha catenin (Supplementary Table S2, Supplementary Fig. S7A). The gene discussed is SIRT1; the disease is rheumatoid arthritis.