EPIFBMC: A New Model for Enhancer–Promoter Interaction Prediction

Enhancer-promoter interactions (EPIs) play a key role in epigenetic regulation of gene expression, dominating cellular identity and functional diversity. Dissecting these interactions is crucial for understanding transcriptional regulatory networks and their significance in cell differentiation, development, and disease. Here, we propose a novel deep learning framework, EPIFBMC (Enhancer-Promoter Interaction prediction with FBMC network) that leverages DNA sequence and genomic features for accurate EPI prediction. The FBMC network consists of three key modules: the Four-Encoding module first encodes the DNA sequence in multiple dimensions to extract key sequence information; then the BESL (Balanced Ensemble Subset Learning) adopts an integrated subset learning strategy to optimize the feature-learning process of positive and negative samples; finally, the MCANet module completes the training of EPI prediction based on a Multi-channel Network. We evaluated EPIFBMC on three cell line datasets (HeLa, IMR90, and NHEK), and validated its generalizability across three independent datasets (K562, GM12878, HUVEC) through cross-cell-line experiments, comparing favorably with state-of-the-art methods. Notably, EPIFBMC balances genomic feature richness and computational complexity, significantly accelerating training speed. Ablation studies identified two key DNA sequence features-positional conservation and positional specificity score-which showed critical predictive value across a benchmark dataset of six diverse cell lines. The computational testing show that EPIFBMC shows excellent performance in the EPI prediction task, providing a powerful tool for decoding gene regulatory networks. It is believed that it will have important application prospects in developmental biology, disease mechanism research, and therapeutic target discovery.