GNAEMDA: Microbe-Drug Associations Prediction on Graph Normalized Convolutional Network

The importance of microbe-drug associations (MDA) prediction is evidenced in research. Since traditional wet-lab experiments are both time-consuming and costly, computational methods are widely adopted. However, existing research has yet to consider the cold-start scenarios that commonly seen in real-world clinical research and practices where data of confirmed microbe-drug associations are highly sparse. Therefore, we aim to contribute by developing two novel computational approaches, the GNAEMDA (Graph Normalized Auto-Encoder to predict Microbe-Drug Associations), and a variational extension of the GNAEMDA (called VGNAEMDA), to provide effective and efficient solutions for well-annotated cases and cold-start scenarios. Multi-modal attribute graphs are constructed by collecting multiple features of microbes and drugs, and then input into a graph normalized convolutional network, where a l2-normalization is introduced to avoid the norm-towards-zero tendency of isolated nodes in embedding space. Then the reconstructed graph output by the network is used to infer undiscovered MDA. The difference between the proposed two models lays in the way to generate the latent variables in network. To verify the effectiveness of the two proposed models, we conduct a series of experiments on three benchmark datasets in comparison with six state-of-the-art methods. The comparison results indicate that both GNAEMDA and VGNAEMDA have strong prediction performances in all cases, especially in identifying associations for new microbes or drugs. In addition, we conduct case studies on two drugs and two microbes and find that more than 75% of the predicted associations have been reported in PubMed. The comprehensive experimental results validate the reliability of our models in accurately inferring potential MDA.