Circular RNAs (circRNAs) are a newly identified type of non-coding RNA (ncRNA) that plays crucial roles in many cellular processes and human diseases, and are potential disease biomarkers and therapeutic targets in human diseases. However, experimentally verified circRNA-disease associations are very rare. Hence, developing an accurate and efficient method to predict the association between circRNA and disease may be beneficial to disease prevention, diagnosis, and treatment. Here, we propose a computational method named KATZCPDA, which is based on the KATZ method and the integrations among circRNAs, proteins, and diseases to predict circRNA-disease associations. KATZCPDA not only verifies existing circRNA-disease associations but also predicts unknown associations. As demonstrated by leave-one-out and 10-fold cross-validation, KATZCPDA achieves AUC values of 0.959 and 0.958, respectively. The performance of KATZCPDA was substantially higher than those of previously developed network-based methods. To further demonstrate the effectiveness of KATZCPDA, we apply KATZCPDA to predict the associated circRNAs of Colorectal cancer, glioma, breast cancer, and Tuberculosis. The results illustrated that the predicted circRNA-disease associations could rank the top 10 of the experimentally verified associations.

Background RNA binding proteins (RBPs) play a vital role in post-transcriptional processes in all eukaryotes, such as splicing regulation, mRNA transport, and modulation of mRNA translation and decay. The identification of RBP binding sites is a crucial step in understanding the biological mechanism of post-transcriptional gene regulation. However, the determination of RBP binding sites on a large scale is a challenging task due to high cost of biochemical assays. Quite a number of studies have exploited machine learning methods to predict binding sites. Especially, deep learning is increasingly used in the bioinformatics field by virtue of its ability to learn generalized representations from DNA and protein sequences. Results In this paper, we implemented a novel deep neural network model, DeepRKE, which combines primary RNA sequence and secondary structure information to effectively predict RBP binding sites. Specifically, we used word embedding algorithm to extract features of RNA sequences and secondary structures, i.e., distributed representation of k-mers sequence rather than traditional one-hot encoding. The distributed representations are taken as input of convolutional neural networks (CNN) and bidirectional long-term short-term memory networks (BiLSTM) to identify RBP binding sites. Our results show that deepRKE outperforms existing counterpart methods on two large-scale benchmark datasets. Conclusions Our extensive experimental results show that DeepRKE is an efficacious tool for predicting RBP binding sites. The distributed representations of RNA sequences and secondary structures can effectively detect the latent relationship and similarity between k-mers, and thus improve the predictive performance. The source code of DeepRKE is available at https://github.com/youzhiliu/DeepRKE/.

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