Fig. 1

Topological modeling approach of signaling pathways for prediction of combination therapy. a Identification of subgroup networks. A model characterizing signaling activity (upstream kinase (circle) that regulates a response, e.g., innate immunity, survival (diamond)) in response to a stimulus (oval) was calculated for each donor based on the experimentally acquired dataset. Next, the donor-specific models are merged for all donors belonging to the same subgroup (left panel blue: healthy controls; middle panel orange: untreated MS; right panel green: treated MS). b Scoring subgroup interactions to find co-druggable network interactions. The score is calculated to identify interactions that differ from healthy-like signaling activity in spite of drug treatment (see the “Methods” section). c Topological prediction of drug combination. A topology-based graph search allows identifying secondary treatments that could target and revert signaling of co-druggable interactions to a healthy-like activity state