EnContact: predicting enhancer-enhancer contacts using sequence-based deep learning model

Chromatin contacts between regulatory elements are of crucial importance for the interpretation of transcriptional regulation and the understanding of disease mechanisms. However, existing computational methods mainly focus on the prediction of interactions between enhancers and promoters, leaving enhancer-enhancer (E-E) interactions not well explored. In this work, we develop a novel deep learning approach, named Enhancer-enhancer contacts prediction (EnContact), to predict E-E contacts using genomic sequences as input. We statistically demonstrated the predicting ability of EnContact using training sets and testing sets derived from HiChIP data of seven cell lines. We also show that our model significantly outperforms other baseline methods. Besides, our model identifies finer-mapping E-E interactions from region-based chromatin contacts, where each region contains several enhancers. In addition, we identify a class of hub enhancers using the predicted E-E interactions and find that hub enhancers tend to be active across cell lines. We summarize that our EnContact model is capable of predicting E-E interactions using features automatically learned from genomic sequences.