CircWalk: A novel approach to predict CircRNA- Disease association based on heterogeneous network representation learning

Abstract

Background: Several types of RNA in the cell are usually involved in biological processes with multiple functions. Generally, coding RNAs translate to proteins, and non-coding ones regulate this translation in the gene regulatory networks. Some single-strand RNAs can create a circular shape via the back splicing process and convert into a new type called circular RNA (circRNA). circRNAs are among the most important non-coding RNAs in the cell that involve multiple disorders. One of the key functions of circRNAs is to regulate the expression of other genes through sponging micro RNAs (miRNAs) in diseases. This mechanism, known as the competing endogenous RNA (ceRNA) hypothesis, and additional information obtained from biological datasets can be used by computational approaches to predict novel associations between disease and circRNAs. Results: We applied multiple classifiers to validate the extracted features from the heterogeneous network and selected the best one based on some evaluation criteria. Then, the XGBoost is utilized in our pipeline to generate a novel approach, called CircWalk, to predict CircRNA-Disease associations. Our results demonstrate that CircWalk has reasonable accuracy and AUC compared with other state-of-the-art algorithms. We also use CircWalk to predict novel circRNAs associated with lung, gastric, and colorectal cancers as a case study. The results show that our approach can accurately predict novel circRNAs related to these diseases. Conclusions: In this study, considering the ceRNA hypothesis, we integrate multiple resources to construct a heterogeneous network from circRNAs, mRNAs, miRNAs, and diseases. Next, the DeepWalk algorithm is applied to the network to extract feature vectors for circRNAs and diseases. The extracted features are used to learn a classifier and generate a model to predict novel CircRNA-Disease associations. Our approach uses the concept of the ceRNA hypothesis and the miRNA sponge effect of circRNAs to predict their associations with diseases. Our results show that this outlook could help anticipate CircRNA-Disease associations more accurately.