Background: With the rapid development of deep sequencing techniques in the recent years, enhancers have been systematically identified in such projects as FANTOM and ENCODE, forming genome-wide landscapes in a series of human cell lines. Nevertheless, experimental approaches are still costly and time consuming for large scale identification of enhancers across a variety of tissues under different disease status, making computational identification of enhancers indispensable.
Results: To facilitate the identification of enhancers, we propose a computational framework, named DeepEnhancer, to distinguish enhancers from background genomic sequences. Our method purely relies on DNA sequences to predict enhancers in an end-to-end manner by using a deep convolutional neural network (CNN). We train our deep learning model on permissive enhancers and then adopt a transfer learning strategy to fine-tune the model on enhancers specific to a cell line. Results demonstrate the effectiveness and efficiency of our method in the classification of enhancers against random sequences, exhibiting advantages of deep learning over traditional sequence-based classifiers. We then construct a variety of neural networks with different architectures and show the usefulness of such techniques as max-pooling and batch normalization in our method. To gain the interpretability of our approach, we further visualize convolutional kernels as sequence logos and successfully identify similar motifs in the JASPAR database.
Conclusions: DeepEnhancer enables the identification of novel enhancers using only DNA sequences via a highly accurate deep learning model. The proposed computational framework can also be applied to similar problems, thereby prompting the use of machine learning methods in life sciences.