MSDSE: Predicting drug-side effects based on multi-scale features and deep multi-structure neural network.

Unexpected side effects may accompany the research stage and post-marketing of drugs. These accidents lead to drug development failure and even endanger patients' health. Thus, it is essential to recognize the unknown drug-side effects. Most existing methods in silico find the answer from the association network or similarity network of drugs while ignoring the drug-intrinsic attributes. The limitation is that they can only handle drugs in the maturation stage. To be suitable for early drug-side effect screening, we conceive a multi-structural deep learning framework, MSDSE, which synthetically considers the multi-scale features derived from the drug. MSDSE can jointly learn SMILES sequence-based word embedding, substructure-based molecular fingerprint, and chemical structure-based graph embedding. In the preprocessing stage of MSDSE, we project all features to the abstract space with the same dimension. MSDSE builds a bi-level channel strategy, including a convolutional neural network module with an Inception structure and a multi-head Self-Attention module, to learn and integrate multi-modal features from local to global perspectives. Finally, MSDSE regards the prediction of drug-side effects as pair-wise learning and outputs the pair-wise probability of drug-side effects through the inner product operation. MSDSE is evaluated and analyzed on benchmark datasets and performs optimally compared to other baseline models. We also set up the ablation study to explain the rationality of the feature approach and model structure. Moreover, we select model partial prediction results for the case study to reveal actual capability. The original data are available at http://github.com/yuliyi/MSDSE.