Evaluating disease similarity based on gene network reconstruction and representation

Abstract Motivation Quantifying the associations between diseases is of great significance in increasing our understanding of disease biology, improving disease diagnosis, re-positioning and developing drugs. Therefore, in recent years, the research of disease similarity has received a lot of attention in the field of bioinformatics. Previous work has shown that the combination of the ontology (such as disease ontology and gene ontology) and disease–gene interactions are worthy to be regarded to elucidate diseases and disease associations. However, most of them are either based on the overlap between disease-related gene sets or distance within the ontology’s hierarchy. The diseases in these methods are represented by discrete or sparse feature vectors, which cannot grasp the deep semantic information of diseases. Recently, deep representation learning has been widely studied and gradually applied to various fields of bioinformatics. Based on the hypothesis that disease representation depends on its related gene representations, we propose a disease representation model using two most representative gene resources HumanNet and Gene Ontology to construct a new gene network and learn gene (disease) representations. The similarity between two diseases is computed by the cosine similarity of their corresponding representations. Results We propose a novel approach to compute disease similarity, which integrates two important factors disease-related genes and gene ontology hierarchy to learn disease representation based on deep representation learning. Under the same experimental settings, the AUC value of our method is 0.8074, which improves the most competitive baseline method by 10.1%. The quantitative and qualitative experimental results show that our model can learn effective disease representations and improve the accuracy of disease similarity computation significantly. Availability and implementation The research shows that this method has certain applicability in the prediction of gene-related diseases, the migration of disease treatment methods, drug development and so on. Supplementary information Supplementary data are available at Bioinformatics online.