Network-based in silico drug efficacy screening

The increasing cost of drugdevelopment together with a significant drop in the number of new drugapprovals raises the need for innovative approaches for target identification and efficacy prediction. Here, we take advantage of our increasing understanding of the network-based origins of diseases to introduce a drug-disease proximity measure that quantifies the interplay between drugstargets and diseases. By correcting for the known biases of the interactome, proximity helps us uncover the therapeutic effectof drugs, as well as to distinguish palliative from effective treatments. Our analysis of 238 drugsused in 78 diseases indicates that the therapeutic effectof drugsis localized in a small network neighborhood of the disease genes and highlights efficacy issues for drugsused in Parkinson and several inflammatory disorders. Finally, network-based proximity allows us to predict novel drug-disease associations that offer unprecedented opportunities for drug repurposingand the detection of adverse effects.