Enhancer target prediction: state-of-the-art approaches and future prospects

Enhancers are genomic regions that regulate gene transcription and are located far away from the transcription start sites of their target genes. Enhancers are highly enriched in disease-associated variants and thus deciphering the interactions between enhancers and genes is crucial to understanding the molecular basis of genetic predispositions to diseases. Experimental validations of enhancer targets can be laborious. Computational methods have thus emerged as a valuable alternative for studying enhancer-gene interactions. A variety of computational methods have been developed to predict enhancer targets by incorporating genomic features (e.g. conservation, distance, and sequence), epigenomic features (e.g. histone marks and chromatin contacts) and activity measurements (e.g. covariations of enhancer activity and gene expression). With the recent advances in genome perturbation and chromatin conformation capture technologies, data on experimentally validated enhancer targets are becoming available for supervised training of these methods and evaluation of their performance. In this review, we categorize enhancer target prediction methods based on their rationales and approaches. Then we discuss their merits and limitations and highlight the future directions for enhancer targets prediction.