Fig. 4: CytoSig predicts cytokine activities in human diseases.
From: Systematic investigation of cytokine signaling activity at the tissue and single-cell levels
a, IL-1β activities in blood predicted the anti-IL-1β therapy response in arthritis. Each dot represents a blood sample35. The x axis shows patients with similar therapy responses. The y axis shows the IL-1β activities predicted by CytoSig at an early time point, shown by violin plots smoothed by a kernel density estimator. Spearman correlation between clinical response in patient groups and the median IL-1β activity with a two-sided t-test P value is indicated. b, IFN-I activity in blood correlated with antibody titer upon IFN-α vaccine in patients with systemic lupus. Each dot represents a blood sample. The x axis presents the titer of IFN-α antibody after immunization36. The y axis presents the IFN-I differential activity predicted by CytoSig. Spearman correlation between x and y axes with a two-sided t-test P value is indicated (n = 36). c, Predicted activity change upon anti-cytokine therapies. Each dot represents an anti-cytokine therapy study in inflammatory diseases, with targets on the x axis. Gray labels represent mouse model studies for cytokines without clinical data. The y axis presents the average differential activity between posttreatment and pretreatment groups. The accuracy was computed as the fraction of cytokines with median activity reduction smaller than one, with P value from the two-sided Wilcoxon signed-rank test. d, TGF-β activity changes upon neutralizing antibody treatments. The first antibody inhibited all TGF-β isoforms (123; n = 7 mice) and the second antibody inhibited only TGF-β1 and TGF-β2 (12; n = 6 mice). The anti-TGF-β3 profile (123/12) was the differential profile between the pan-TGF-β- and the TGF-β1/2-specific groups. The TGF-β1 and TGF-β3 activities predicted by CytoSig are shown by bar plots, with two-sided P values from the permutation test with 10,000 randomizations. e, VEGF activities in pretreatment tumors predicted the anti-VEGF therapy response in sunitinib38 and bevacizumab clinical studies39. The Kaplan–Meier plot presents patient fractions (y axis) with survival length (x axis, progression-free or overall) among pretreatment tumors with high and low VEGFA activities predicted by CytoSig. The activity cutoff was selected through maximizing the difference between high and low groups. The P value was derived from the one-sided Wald test using continuous values without cutoffs.
