Fig. 1.
Network-based model of drug–drug relationship. a A subnetwork of the human interactome illustrating the network-based relationship between drug targets associated with three drugs (imatinib [I], tandutinib [T], and natalizumab [N]). b, c The definition of drug pairs that are topologically overlapping (sAB < 0, b) or topologically separated (sAB ≥ 0, c). d–j The interplay between topological separation of drug pairs and five types of drug profiles: drug–drug chemical similarity (d); drug target-encoding gene co-expression pattern across human tissues (e); drug target protein sequence similarity (f). Using the Gene Ontology (GO) annotations, we determine for each drug how similar its associated target-encoding genes are in terms of their biological processes (g), cellular component (h), and molecular function (i); and clinical similarity (j) of drug pairs derived from Anatomical Therapeutic Chemical Classification Systems codes (see Methods). Overlapping drug pairs are highlighted in orange (sAB < 0); topologically separated drug pairs are highlighted in blue (sAB ≥ 0)