Abstract
CRISPR-mediated epigenome editing enables gene expression regulation without changing the underlying DNA sequence, and thus has vast potential for basic research and gene therapy. Effective selection of a single guide RNA (sgRNA) with high on-target efficiency and specificity would facilitate the application of epigenome editing tools. Here we performed an extensive analysis of CRISPR-mediated epigenome editing tools on thousands of experimentally examined on-target sites and established EpiCas-DL, a deep learning framework to optimize sgRNA design for gene silencing or activation. EpiCas-DL achieves high accuracy in sgRNA activity prediction for targeted gene silencing or activation and outperforms other available in silico methods. In addition, EpiCas-DL also identifies both epigenetic and sequence features that affect sgRNA efficacy in gene silencing and activation, facilitating the application of epigenome editing for research and therapy. EpiCas-DL is available at http://www.sunlab.fun:3838/EpiCas-DL.