Graph Convolutional Neural Network with Multi-Layer Attention Mechanism for Predicting Potential Microbe-Disease Associations

Background: Human microbial communities play an important role in some physiological process of human beings. Nevertheless, the identification of microbe-disease associations through biological experiments is costly and time-consuming. Hence, the development of calculation models is meaningful to infer latent associations between microbes and diseases. Aims: In this manuscript, we aim to design a computational model based on the Graph Convolutional Neural Network with Multi-layer Attention mechanism, called GCNMA, to infer latent microbe-disease associations. Objective: This study aims to propose a novel computational model based on the Graph Convolutional Neural Network with Multi-layer Attention mechanism, called GCNMA, to detect potential microbedisease associations. Methods: In GCNMA, the known microbe-disease association network was first integrated with the microbe- microbe similarity network and the disease-disease similarity network into a heterogeneous network first. Subsequently, the graph convolutional neural network was implemented to extract embedding features of each layer for microbes and diseases respectively. Thereafter, these embedding features of each layer were fused together by adopting the multi-layer attention mechanism derived from the graph convolutional neural network, based on which, a bilinear decoder would be further utilized to infer possible associations between microbes and diseases. Results: Finally, to evaluate the predictive ability of GCNMA, intensive experiments were done and compared results with eight state-of-the-art methods which demonstrated that under the frameworks of both 2-fold cross-validations and 5-fold cross-validations, GCNMA can achieve satisfactory prediction performance based on different databases including HMDAD and Disbiome simultaneously. Moreover, case studies on three kinds of common diseases such as asthma, type 2 diabetes, and inflammatory bowel disease verified the effectiveness of GCNMA as well. Conclusion: GCNMA outperformed 8 state-of-the-art competitive methods based on the benchmarks of both HMDAD and Disbiome.