Introducing TEC-LncMir for prediction of lncRNA-miRNA interactions through deep learning of RNA sequences

The interactions between long noncoding RNA (lncRNA) and microRNA (miRNA) play critical roles in life processes, highlighting the necessity to enhance the performance of state-of-the-art models. Here, we introduced TEC-LncMir, a novel approach for predicting lncRNA-miRNA interaction using Transformer Encoder and convolutional neural networks (CNNs). TEC-LncMir treats lncRNA and miRNA sequences as natural languages, encodes them using the Transformer Encoder, and combines representations of a pair of microRNA and lncRNA into a contact tensor (a three-dimensional array). Afterward, TEC-LncMir treats the contact tensor as a multi-channel image, utilizes a four-layer CNN to extract the contact tensor's features, and then uses these features to predict the interaction between the pair of lncRNA and miRNA. We applied a series of comparative experiments to demonstrate that TEC-LncMir significantly improves lncRNA-miRNA interaction prediction, compared with existing state-of-the-art models. We also trained TEC-LncMir utilizing a large training dataset, and as expected, TEC-LncMir achieves unprecedented performance. Moreover, we integrated miRanda into TEC-LncMir to show the secondary structures of high-confidence interactions. Finally, we utilized TEC-LncMir to identify microRNAs interacting with lncRNA NEAT1, where NEAT1 performs as a competitive endogenous RNA of the microRNAs' targets (mRNAs) in brain cells. We also demonstrated the regulatory mechanism of NEAT1 in Alzheimer's disease via transcriptome analysis and sequence alignment analysis. Overall, our results demonstrate the effectivity of TEC-LncMir, suggest a potential regulation of miRNAs by NEAT1 in Alzheimer's disease, and take a significant step forward in lncRNA-miRNA interaction prediction.