DeepNC: a framework for drug-target interaction prediction with graph neural networks

PeerJ. 2022 May 11;10:e13163. doi: 10.7717/peerj.13163. eCollection 2022.


The exploration of drug-target interactions (DTI) is an essential stage in the drug development pipeline. Thanks to the assistance of computational models, notably in the deep learning approach, scientists have been able to shorten the time spent on this stage. Widely practiced deep learning algorithms such as convolutional neural networks and recurrent neural networks are commonly employed in DTI prediction projects. However, they can hardly utilize the natural graph structure of molecular inputs. For that reason, a graph neural network (GNN) is an applicable choice for learning the chemical and structural characteristics of molecules when it represents molecular compounds as graphs and learns the compound features from those graphs. In an effort to construct an advanced deep learning-based model for DTI prediction, we propose Deep Neural Computation (DeepNC), which is a framework utilizing three GNN algorithms: Generalized Aggregation Networks (GENConv), Graph Convolutional Networks (GCNConv), and Hypergraph Convolution-Hypergraph Attention (HypergraphConv). In short, our framework learns the features of drugs and targets by the layers of GNN and 1-D convolution network, respectively. Then, representations of the drugs and targets are fed into fully-connected layers to predict the binding affinity values. The models of DeepNC were evaluated on two benchmarked datasets (Davis, Kiba) and one independently proposed dataset (Allergy) to confirm that they are suitable for predicting the binding affinity of drugs and targets. Moreover, compared to the results of baseline methods that worked on the same problem, DeepNC proves to improve the performance in terms of mean square error and concordance index.

Keywords: Binding affinity; Cheminformatics; Deep learning; Drug discovery; Drug-target interaction; Graph neural networks.

Grant support

This work is supported by the Fundamental Research Grant Scheme (FRGS) of the Ministry of Higher Education Malaysia under the grant project number FRGS/1/2019/ICT02/KDUPG/02/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.