CellCircLoc: Deep Neural Network for Predicting and Explaining Cell Line-Specific CircRNA Subcellular Localization.

Abstract

The subcellular localization of circular RNAs (circRNAs) is crucial for understanding their functional relevance and regulatory mechanisms. CircRNA subcellular localization exhibits variations across different cell lines, demonstrating the diversity and complexity of circRNA regulation within distinct cellular contexts. However, existing computational methods for predicting circRNA subcellular localization often ignore the importance of cell line specificity and instead train a general model on aggregated data from all cell lines. Considering the diversity and context-dependent behavior of circRNAs across different cell lines, it is imperative to develop cell line-specific models to accurately predict circRNA subcellular localization. In the study, we proposed CellCircLoc, a sequence-based deep learning model for circRNA subcellular localization prediction, which is trained for different cell lines. CellCircLoc utilizes a combination of convolutional neural networks, Transformer blocks, and bidirectional long short-term memory to capture both sequence local features and long-range dependencies within the sequences. In the Transformer blocks, CellCircLoc uses an attentive convolution mechanism to capture the importance of individual nucleotides. Extensive experiments demonstrate the effectiveness of CellCircLoc in accurately predicting circRNA subcellular localization across different cell lines, outperforming other computational models that do not consider cell line specificity. Moreover, the interpretability of CellCircLoc facilitates the discovery of important motifs associated with circRNA subcellular localization. The CellCircLoc web server is available at http://csuligroup.com:8000/cellcircloc. The source code can be obtained from https://github.com/CSUBioGroup/CellCircLoc.