Fig. 1: Synovial signature of response to biologics at baseline.
a, c, e Volcano plots of differentially expressed genes from DESeq2 analysis of RNA-sequencing of baseline synovial biopsies of rheumatoid arthritis individuals receiving treatment with a etanercept (n = 67), c tocilizumab (n = 69) or e rituximab (n = 72) comparing ACR20 responders vs non-responders at the 16-week primary endpoint. DESeq2 statistical analysis uses generalised linear modelling of count data using the negative binomial distribution. The model included a single covariate based on principal component analysis applied to 17 muscle tissue-specific genes (see Methods). P values were calculated by a two-sided Wald test with FDR correction (Storey’s q value) for multiple testing. Genes in blue are significant at FDR <0.05, genes in grey are non-significant. b, d, f Modular analysis applying QuSAGE statistical testing with blood-derived gene modules (Li et al., 2014) and synovium-derived WGCNA modules for 16-week ACR20 responders versus non-responders to etanercept (b), tocilizumab (d) and rituximab (f). Log2-fold change of responders (positive values) and non-responders (negative values) are plotted with dots colour coded for unadjusted p value.
