Prediction of enhancer-promoter interactions via natural language processing

Abstract

Background: Precise identification of three-dimensional genome organization, especially enhancer-promoter interactions (EPIs), is important to deciphering gene regulation, cell differentiation and disease mechanisms. Currently, it is a challenging task to distinguish true interactions from other nearby non-interacting ones since the power of traditional experimental methods is limited due to low resolution or low throughput. Results: We propose a novel computational framework EP2vec to assay three-dimensional genomic interactions. We first extract sequence embedding features, defined as fixed-length vector representations learned from variable-length sequences using an unsupervised deep learning method in natural language processing. Then, we train a classifier to predict EPIs using the learned representations in supervised way. Experimental results demonstrate that EP2vec obtains F1 scores ranging from 0.841~0.933 on different datasets, which outperforms existing methods. We prove the robustness of sequence embedding features by carrying out sensitivity analysis. Besides, we identify motifs that represent cell line-specific information through analysis of the learned sequence embedding features by adopting attention mechanism. Last, we show that even superior performance with F1 scores 0.889~0.940 can be achieved by combining sequence embedding features and experimental features. Conclusions: EP2vec sheds light on feature extraction for DNA sequences of arbitrary lengths and provides a powerful approach for EPIs identification.