In silico drug-target interaction (DTI) prediction is an important and challenging problem in biomedical research with a huge potential benefit to the pharmaceutical industry and patients. Most existing methods for DTI prediction including deep learning models generally have binary endpoints, which could be an oversimplification of the problem, and those methods are typically unable to handle cold-target problems, i.e., problems involving target protein that never appeared in the training set. Towards this, we contrived PADME (Protein And Drug Molecule interaction prEdiction), a framework based on Deep Neural Networks, to predict real-valued interaction strength between compounds and proteins without requiring feature engineering. PADME takes both compound and protein information as inputs, so it is capable of solving cold-target (and cold-drug) problems. To our knowledge, we are the first to combine Molecular Graph Convolution (MGC) for compound featurization with protein descriptors for DTI prediction. We used multiple cross-validation split schemes and evaluation metrics to measure the performance of PADME on multiple datasets, including the ToxCast dataset, which we believe should be a standard benchmark for DTI problems, and PADME consistently dominates baseline methods. The results of a case study, which predicts the binding affinity between various compounds and androgen receptor (AR), suggest PADME's potential in drug development. The scalability of PADME is another advantage in the age of Big Data.
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Thesis advisor: Ester, Martin
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