 A drug combination is usually classified as synergistic or antagonistic, depending on the deviation of the observed combination response from the expected effect calculated based on a reference model of non-interaction. The existing reference models were proposed originally for low-throughput drug combination experiments. We proposed a novel reference model, named zero interaction potency, ZIP, which captures the drug interaction relationships by comparing the change in the potency of the dose response curves between individual drugs and their combinations. This article was authored by Bugvanyadov, Krzysztof Wennerberg, Tarou Adokalio, and others.