Title: Modeling polypharmacy side effects with graph convolutional networks,
Abstract: The use of drug combinations, termed polypharmacy, is common to treat
patients with complex diseases and co-existing conditions. However, a major
consequence of polypharmacy is a much higher risk of adverse side effects for
the patient. Polypharmacy side effects emerge because of drug-drug
interactions, in which activity of one drug may change if taken with another
drug. The knowledge of drug interactions is limited because these complex
relationships are rare, and are usually not observed in relatively small
clinical testing. Discovering polypharmacy side effects thus remains an
important challenge with significant implications for patient mortality. Here,
we present Decagon, an approach for modeling polypharmacy side effects. The
approach constructs a multimodal graph of protein-protein interactions,
drug-protein target interactions, and the polypharmacy side effects, which are
represented as drug-drug interactions, where each side effect is an edge of a
different type. Decagon is developed specifically to handle such multimodal
graphs with a large number of edge types. Our approach develops a new graph
convolutional neural network for multirelational link prediction in multimodal
networks. Decagon predicts the exact side effect, if any, through which a given
drug combination manifests clinically. Decagon accurately predicts polypharmacy
side effects, outperforming baselines by up to 69%. We find that it
automatically learns representations of side effects indicative of
co-occurrence of polypharmacy in patients. Furthermore, Decagon models
particularly well side effects with a strong molecular basis, while on
predominantly non-molecular side effects, it achieves good performance because
of effective sharing of model parameters across edge types. Decagon creates
opportunities to use large pharmacogenomic and patient data to flag and
prioritize side effects for follow-up analysis.