A Pretraining-Retraining Strategy of Deep Learning Improves Cell-Specific Enhancer Predictions.

Deciphering the code of cis-regulatory element (CRE) is one of the core issues of today's biology. Enhancers are distal CREs and play significant roles in gene transcriptional regulation. Although identifications of enhancer locations across the whole genome [discriminative enhancer predictions (DEP)] is necessary, it is more important to predict in which specific cell or tissue types, they will be activated and functional [tissue-specific enhancer predictions (TSEP)]. Although existing deep learning models achieved great successes in DEP, they cannot be directly employed in TSEP because a specific cell or tissue type only has a limited number of available enhancer samples for training. Here, we first adopted a reported deep learning architecture and then developed a novel training strategy named "pretraining-retraining strategy" (PRS) for TSEP by decomposing the whole training process into two successive stages: a pretraining stage is designed to train with the whole enhancer data for performing DEP, and a retraining strategy is then designed to train with tissue-specific enhancer samples based on the trained pretraining model for making TSEP. As a result, PRS is found to be valid for DEP with an AUC of 0.922 and a GM (geometric mean) of 0.696, when testing on a larger-scale FANTOM5 enhancer dataset

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Copyright © 2020 Niu, Yang, Zhang, Yang and Hu.