Abstract
Piwi-interacting RNA (piRNA) is a type of non-coding small RNA that is highly expressed in mammalian testis. PiRNA has been implicated in various human diseases, but the experimental validation of piRNA-disease associations is costly and time-consuming. In this article, a novel computational method for predicting piRNA-disease associations using a multi-channel graph variational autoencoder (MC-GVAE) is proposed. This method integrates four types of similarity networks for piRNAs and diseases, which are derived from piRNA sequences, disease semantics, piRNA Gaussian Interaction Profile (GIP) kernel, and disease GIP kernel, respectively. These networks are modeled by a graph VAE framework, which can learn low-dimensional and informative feature representations for piRNAs and diseases. Then, a multi-channel method is used to fuse the feature representations from different networks. Finally, a three-layer neural network classifier is applied to predict the potential associations between piRNAs and diseases. The method was evaluated on a benchmark dataset containing 5,002 experimentally validated associations with 4,350 piRNAs and 21 diseases, constructed from the piRDisease v1.0 database. It achieved state-of-the-art performance, with an average AUC value of 0.9310 and an AUPR value of 0.9247 under five-fold cross-validation. This demonstrates the method's effectiveness and superiority in piRNA-disease association prediction.