EPIsHilbert: Prediction of Enhancer-Promoter Interactions via Hilbert Curve Encoding and Transfer Learning

Enhancer-promoter interactions (EPIs) play a significant role in the regulation of gene transcription. However, enhancers may not necessarily interact with the closest promoters, but with distant promoters via chromatin looping. Considering the spatial position relationship between enhancers and their target promoters is important for predicting EPIs. Most existing methods only consider sequence information regardless of spatial information. On the other hand, recent computational methods lack generalization capability across different cell line datasets. In this paper, we propose EPIsHilbert, which uses Hilbert curve encoding and two transfer learning approaches. Hilbert curve encoding can preserve the spatial position information between enhancers and promoters. Additionally, we use visualization techniques to explore important sequence fragments that have a high impact on EPIs and the spatial relationships between them. Transfer learning can improve prediction performance across cell lines. In order to further prove the effectiveness of transfer learning, we analyze the sequence coincidence of different cell lines. Experimental results demonstrate that EPIsHilbert is a state-of-the-art model that is superior to most of the existing methods both in specific cell lines and cross cell lines.