DeepCORE: An interpretable multi-view deep neural network model to detect co-operative regulatory elements

Gene transcription is an essential process involved in all aspects of cellular functions with significant impact on biological traits and diseases. This process is tightly regulated by multiple elements that co-operate to jointly modulate the transcription levels of target genes. To decipher the complicated regulatory network, we present a novel multi-view attention-based deep neural network that models the relationship between genetic, epigenetic, and transcriptional patterns and identifies co-operative regulatory elements (COREs). We applied this new method, named DeepCORE, to predict transcriptomes in 25 different cell lines, which outperformed the state-of-the-art algorithms. Furthermore, DeepCORE translates the attention values embedded in the neural network into interpretable information, including locations of putative regulatory elements and their correlations, which collectively implies COREs. These COREs are significantly enriched with known promoters and enhancers. Novel regulatory elements discovered by DeepCORE showed epigenetic signatures consistent with the status of histone modification marks.