Adding Stochastic Negative Examples into Machine Learning Improves Molecular Bioactivity Prediction
Published Web Location
https://pubs.acs.org/doi/10.1021/acs.jcim.0c00565Abstract
Multitask deep neural networks learn to predict ligand-target binding by example, yet public pharmacological data sets are sparse, imbalanced, and approximate. We constructed two hold-out benchmarks to approximate temporal and drug-screening test scenarios, whose characteristics differ from a random split of conventional training data sets. We developed a pharmacological data set augmentation procedure, Stochastic Negative Addition (SNA), which randomly assigns untested molecule-target pairs as transient negative examples during training. Under the SNA procedure, drug-screening benchmark performance increases from R2 = 0.1926 ± 0.0186 to 0.4269 ± 0.0272 (122%). This gain was accompanied by a modest decrease in the temporal benchmark (13%). SNA increases in drug-screening performance were consistent for classification and regression tasks and outperformed y-randomized controls. Our results highlight where data and feature uncertainty may be problematic and how leveraging uncertainty into training improves predictions of drug-target relationships.
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