Integration of pairwise neighbor topologies and miRNA family and cluster attributes for miRNA–disease association prediction

Abstract

Identifying disease-related microRNAs (miRNAs) assists the understanding of disease pathogenesis. Existing research methods integrate multiple kinds of data related to miRNAs and diseases to infer candidate disease-related miRNAs. The attributes of miRNA nodes including their family and cluster belonging information, however, have not been deeply integrated. Besides, the learning of neighbor topology representation of a pair of miRNA and disease is a challenging issue. We present a disease-related miRNA prediction method by encoding and integrating multiple representations of miRNA and disease nodes learnt from the generative and adversarial perspective. We firstly construct a bilayer heterogeneous network of miRNA and disease nodes, and it contains multiple types of connections among these nodes, which reflect neighbor topology of miRNA–disease pairs, and the attributes of miRNA nodes, especially miRNA-related families and clusters. To learn enhanced pairwise neighbor topology, we propose a generative and adversarial model with a convolutional autoencoder-based generator to encode the low-dimensional topological representation of the miRNA–disease pair and multi-layer convolutional neural network-based discriminator to discriminate between the true and false neighbor topology embeddings. Besides, we design a novel feature category-level attention mechanism to learn the various importance of different features for final adaptive fusion and prediction. Comparison results with five miRNA–disease association methods demonstrated the superior performance of our model and technical contributions in terms of area under the receiver operating characteristic curve and area under the precision-recall curve. The results of recall rates confirmed that our model can find more actual miRNA–disease associations among top-ranked candidates. Case studies on three cancers further proved the ability to detect potential candidate miRNAs.