3D graph neural network with few-shot learning for predicting drug–drug interactions in scaffold-based cold start scenario

Abstract

Understanding drug–drug interactions (DDI) of new drugs is critical for minimizing unexpected adverse drug reactions. The modeling of new drugs is called a cold start scenario. In this scenario, Only a few structural information or physicochemical information about new drug is available. The 3D conformation of drug molecules usually plays a crucial role in chemical properties compared to the 2D structure. 3D graph network with few-shot learning is a promising solution. However, the 3D heterogeneity of drug molecules and the discretization of atomic distributions lead to spatial confusion in few-shot learning. Here, we propose a 3D graph neural network with few-shot learning, Meta3D-DDI, to predict DDI events in cold start scenario. The 3DGNN ensures rotation and translation invariance by calculating atomic pairwise distances, and incorporates 3D structure and distance information in the information aggregation stage. The continuous filter interaction module can continuously simulate the filter to obtain the interaction between the target atom and other atoms. Meta3D-DDI further develops a FSL strategy based on bilevel optimization to transfer meta-knowledge for DDI prediction tasks from existing drugs to new drugs. In addition, the existing cold start setting may cause the scaffold structure information in the training set to leak into the test set. We design scaffold-based cold start scenario to ensure that the drug scaffolds in the training set and test set do not overlap. The extensive experiments demonstrate that our architecture achieves the SOTA performance for DDI prediction under scaffold-based cold start scenario on two real-world datasets. The visual experiment shows that Meta3D-DDI significantly improves the learning for DDI prediction of new drugs. We also demonstrate how Meta3D-DDI can reduce the amount of data required to make meaningful DDI predictions.