Supplementary Figure 6: Analysis of Pi rating for drugs and target genes using L1000 data and disease-specific gene signatures in RA.

a, Schematic overview showing approach to validate Pi rating at the drug and target level. b, Correlation of Pi ratings with disease-relevant activity of a compound (transcriptional similarity between an RA disease gene expression signature and the compound transcriptional profile in PBMCs quantified using Zhang’s connection score), shown at the drug (left) and target (right) level. Spearman rank correlation calculated, with the significance level estimated empirically (randomly sampling 20,000 times). Sensitivity (estimated by removing different percentages of drugs, repeated 100 times) and specificity (estimated by calculating the correlations based on Pi rating in 29 other immune traits listed in Fig. 3a) shown below. Error bars represent standard deviation with the mean centered. c, L1000 data identifying compounds targeting novel targets in RA. Zhang’s connection score quantifies the disease-relevant expression activity of a compound as the transcriptional similarity between the RA disease gene expression signature and the compound transcriptional profile in PBMCs. The significance level (P = 5%) for the connection score estimated by randomized test using the methodology.