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Abstract A central issue in drug risk-benefit assessment is identifying frequencies of side effects in humans. Currently, frequencies are experimentally determined in randomised controlled clinical trials. We present a machine learning framework for computationally predicting frequencies of drug side effects. Our matrix decomposition algorithm learns latent signatures of drugs and side effects that are both reproducible and biologically interpretable. We show the usefulness of our approach on 759 structurally and therapeutically diverse drugs and 994 side effects from all human physiological systems. Our approach can be applied to any drug for which a small number of side effect frequencies have been identified, in order to predict the frequencies of further, yet unidentified, side effects. We show that our model is informative of the biology underlying drug activity: individual components of the drug signatures are related to the distinct anatomical categories of the drugs and to the specific drug routes of administration. 

Methods for phenotype and outcome prediction are largely based on inductive supervised models that use selected biomarkers to make predictions, without explicitly considering the functional relationships between individuals. We introduce a novel network-based approach namedPatient-Net (P-Net)in which biomolecular profiles of patients are modeled in a graph-structured space that represents gene expression relationships between patients. Then a kernel-based semi-supervised transductive algorithm is applied to the graph to explore the overall topology of the graph and to predict the phenotype/clinical outcome of patients. Experimental tests involving several publicly available datasets of patients afflicted with pancreatic, breast, colon and colorectal cancer show that our proposed method is competitive with state-of-the-art supervised and semi-supervised predictive systems. Importantly,P-Netalso provides interpretable models that can be easily visualized to gain clues about the relationships between patients, and to formulate hypotheses about their stratification.