Figure 7

Sensitivity analysis in the ensemble of populations proposes IFNβ-mediated mechanisms that dominate the clinical response to rituximab. Sensitivity analysis was performed by altering the indicated IFNβ-effect in the biosimulation for each VP while administering rituximab, re-running simulations for the entire cohort, and recalculating population-level statistics using the previously calculated axes weight solutions from MAPEL. The populations are ordered along the x-axis by increasing response to rituximab, and the shade indicates the mean ACR-N score for the VP cohort. In the top series, one effect of IFNβ was allowed to respond to the application of rituximab. In the bottom series, one effect of IFNβ was held fixed during the response to the application of rituximab. VPops were primarily sensitive to the effects on IFNβ on macrophage IL-10 synthesis and FLS proliferation.