Unraveling Disease-Associated PIWI-Interacting RNAs with a Contrastive Learning Methods

PIWI-interacting RNAs (piRNAs) are a class of small, non-coding RNAs predominantly expressed in the germ cells of animals and play a crucial role in maintaining genomic integrity, mediating transposon suppression, and ensuring gene stability. Beyond their functions in reproductive cells, piRNAs also play roles in various human diseases, including cancer, suggesting their potential as significant biomarkers critical for disease diagnosis and treatment. Wet-lab methods to identify piRNA-disease associations require substantial resources and are often hit-or-miss. With advancements in computational technologies, an increasing number of researchers are employing computational methods to efficiently predict potential piRNA-disease associations. The sparsity of data in piRNA-disease association studies significantly limits model performance improvement. In this study, we propose a novel computational model, iPiDA_CL, to predict potential piRNA-disease associations through contrastive learning methods, which do not require negative samples. The model represents piRNA-disease association pairs as a bipartite graph and computes the initial embeddings of piRNAs and diseases using Gaussian kernel similarity, with features updated via LightGCN. Based on the siamese network framework, iPiDA_CL constructs online and target networks and employs data augmentation in the target network to build a contrastive learning objective that optimizes model parameters without introducing negative samples. Finally, cross-prediction methods are used to calculate specific piRNA-disease association scores. A series of experimental results demonstrate that iPiDA_CL surpasses state-of-the-art methods in both performance and computational efficiency. The application of iPiDA_CL to the miRNA-disease association dataset underscores its versatility across various ncRNA-disease association task. Furthermore, a case study highlights iPiDA_CL as an efficient and promising tool for predicting piRNA-disease associations.