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Prediction of enhancer-promoter interactions via natural language processing.


ABSTRACT: BACKGROUND:Precise identification of three-dimensional genome organization, especially enhancer-promoter interactions (EPIs), is important to deciphering gene regulation, cell differentiation and disease mechanisms. Currently, it is a challenging task to distinguish true interactions from other nearby non-interacting ones since the power of traditional experimental methods is limited due to low resolution or low throughput. RESULTS:We propose a novel computational framework EP2vec to assay three-dimensional genomic interactions. We first extract sequence embedding features, defined as fixed-length vector representations learned from variable-length sequences using an unsupervised deep learning method in natural language processing. Then, we train a classifier to predict EPIs using the learned representations in supervised way. Experimental results demonstrate that EP2vec obtains F1 scores ranging from 0.841~ 0.933 on different datasets, which outperforms existing methods. We prove the robustness of sequence embedding features by carrying out sensitivity analysis. Besides, we identify motifs that represent cell line-specific information through analysis of the learned sequence embedding features by adopting attention mechanism. Last, we show that even superior performance with F1 scores 0.889~ 0.940 can be achieved by combining sequence embedding features and experimental features. CONCLUSIONS:EP2vec sheds light on feature extraction for DNA sequences of arbitrary lengths and provides a powerful approach for EPIs identification.

SUBMITTER: Zeng W 

PROVIDER: S-EPMC5954283 | BioStudies | 2018-01-01

SECONDARY ACCESSION(S): GM12878

REPOSITORIES: biostudies

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