Fig. 3

Logic modeling identifies donor-specific signaling networks and reveals MS-specific signaling pathways. a Signaling network found by modeling for each donor, visualized as a heatmap. Rows: Single donor network. Columns: Signaling activity determined for each interaction by calibrating the PKN shown in Additional file 3: Figure S4 after removing the unidentifiable interactions using the phosphoproteomics dataset of each donor. b After networks were merged by subgroup, the Jaccard distance was used to assess similarity from all donors within each group (selected donors in group legend) to their mean subgroup network (network in X axis) and compare it to the similarity from MS patients to the same group network. Healthy donors (blue) were more similar to the mean healthy network than untreated MS patients (orange). In turn, the distance from both groups of donors to that of the combined signaling activity in all donors (grey) was statistically significant. Distance from treated donors (green) to their mean subgroup network was largely reduced when compared to distance from untreated donors to the treatment’s network, suggesting a strong effect of treatment homogenizing within group signaling. c Differentially activated pathways (see Additional file 1: Supplementary methods) between healthy controls (HC) and untreated MS patients (MS). The models previously calculated for each donor were merged to reveal the common active pathways for controls (blue), untreated MS patients (orange), and both (brown). Gray: Inactive interactions from the MS, immune- and treatment-related network (Additional file 3: Figure S4)