MTDDI: a graph convolutional network framework for predicting Multi-Type Drug-Drug Interactions

Abstract

Although the polypharmacy has both higher therapeutic efficacy and less drug resistance in combating complex diseases, drug-drug interactions (DDIs) may trigger unexpected pharmacological effects, such as side effects, adverse reactions, or even serious toxicity. Thus, it is crucial to identify DDIs and explore its underlying mechanism (e.g., DDIs types) for polypharmacy safety. However, the detection of DDIs in assays is still time-consuming and costly, due to the need of experimental search over a large drug combinational space. Machine learning methods have been proved as a promising and efficient method for preliminary DDI screening. Most shallow learning-based predictive methods focus on whether a drug interacts with another or not. Although deep learning (DL)-based predictive methods address a more realistic screening task for identifying the DDI types, they only predict the DDI types of known DDI, ignoring the structural relationship between DDI entries, and they also cannot reveal the knowledge about the dependence between DDI types. Thus, here we proposed a novel end-to-end deep learning-based predictive method (called MTDDI) to predict DDIs as well as its types, exploring the underlying mechanism of DDIs. MTDDI designs an encoder derived from enhanced deep relational graph convolutional networks to capture the structural relationship between multi-type DDI entries, and adopts the tensor-like decoder to uniformly model both single-fold interactions and multi-fold interactions to reflect the relation between DDI types. The results show that our MTDDI is superior to other state-of-the-art deep learning-based methods. For predicting the multi-type DDIs with unknown DDIs in case of both single-fold DDIs and multi-fold DDIs, we validated the effectiveness and the practical capability of our MTDDI. More importantly, MTDDI can reveal the dependency between DDI types. These crucial observations are beneficial to uncover the mechanism and regularity of DDIs.

Prediction of drug-drug interaction events using graph neural networks based feature extraction

“…Ryu et al 37 presented a deep learning approach based on drug chemical substructures to predict 86 crucial DDI types. Feng et al 38 proposed a novel end-to-end deep learning-based predictive method called MTDDI to predict DDIs as well as their types. Deng et al 4 presented a multimodal deep learning framework that employed multiple drug features to predict 65 categories of DDI events.…”