LAUSR

MOTIVATION An imperative step in drug discovery is the prediction of drug-disease associations (DDAs), which tries to uncover potential therapeutic possibilities for already validated drugs. It is costly and time-consuming to predict DDAs using wet experiments. Graph Neural Networks (GNNs) as an emerging technique have shown superior capacity of dealing with DDA prediction. However, existing GNNs-based DDA prediction methods suffer from sparse supervised signals. As Graph Contrastive Learning (GCL) has shined in mitigating sparse supervised signals, we seek to leverage GCL to enhance the prediction of DDAs. Unfortunately, most conventional GCL-based models corrupt the raw data graph to augment data, which are unsuitable for DDA prediction. Meanwhile, these methods could not model the interactions between nodes effectively, thereby reducing the accuracy of association predictions. RESULTS A model is proposed to tap potential drug candidates for diseases, which is called Similarity Measures based Graph Co-contrastive Learning (SMGCL). For learning embeddings from complicated network topologies, SMGCL includes three essential processes: (i) Constructs three views based on similarities between drugs and diseases and DDA information; (ii) Two graph encoders are performed over the three views, so as to model both local and global topologies simultaneously; (iii) A graph co-contrastive learning method is introduced, which co-trains the representations of nodes to maximize the agreement between them, thus generating high-quality prediction results. Contrastive learning serves as an auxiliary task for improving DDA predictions. Evaluated by cross-validations, SMGCL achieves pleasing comprehensive performances. Further proof of the SMGCL's practicality is provided by case study of Alzheimer's disease. AVAILABILITY AND IMPLEMENTATION https://github.com/Jcmorz/SMGCL. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.