Application of Bidirectional Generative Adversarial Networks to Predict Potential miRNAs Associated With Diseases

Front Genet. 2022 Jul 12:13:936823. doi: 10.3389/fgene.2022.936823. eCollection 2022.

Abstract

Substantial evidence has shown that microRNAs are crucial for biological processes within complex human diseases. Identifying the association of miRNA-disease pairs will contribute to accelerating the discovery of potential biomarkers and pathogenesis. Researchers began to focus on constructing computational models to facilitate the progress of disease pathology and clinical medicine by identifying the potential disease-related miRNAs. However, most existing computational methods are expensive, and their use is limited to unobserved relationships for unknown miRNAs (diseases) without association information. In this manuscript, we proposed a creatively semi-supervised model named bidirectional generative adversarial network for miRNA-disease association prediction (BGANMDA). First, we constructed a microRNA similarity network, a disease similarity network, and Gaussian interaction profile kernel similarity based on the known miRNA-disease association and comprehensive similarity of miRNAs (diseases). Next, an integrated similarity feature network with the full underlying relationships of miRNA-disease pairwise was obtained. Then, the similarity feature network was fed into the BGANMDA model to learn advanced traits in latent space. Finally, we ranked an association score list and predicted the associations between miRNA and disease. In our experiment, a five-fold cross validation was applied to estimate BGANMDA's performance, and an area under the curve (AUC) of 0.9319 and a standard deviation of 0.00021 were obtained. At the same time, in the global and local leave-one-out cross validation (LOOCV), the AUC value and standard deviation of BGANMDA were 0.9116 ± 0.0025 and 0.8928 ± 0.0022, respectively. Furthermore, BGANMDA was employed in three different case studies to validate its prediction capability and accuracy. The experimental results of the case studies showed that 46, 46, and 48 of the top 50 prediction lists had been identified in previous studies.

Keywords: MiRNA–disease association prediction; bidirectional generative adversarial network; complex disease; microRNAs; similarity network.