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.

CRISPR介导的表观基因组编辑能够在不改变底层DNA序列的情况下实现基因表达调控，因此在基础研究和基因治疗方面具有巨大的潜力。有效选择具有高靶向效率和特异性的单一指导RNA（sgRNA）将有助于表观基因组编辑工具的应用。在这里，我们对数千个经过实验检查的目标位点进行了 CRISPR 介导的表观基因组编辑工具的广泛分析，并建立了EpiCas-DL ，这是一个深度学习框架，用于优化基因沉默或激活的 sgRNA 设计。 EpiCas-DL在目标基因沉默或激活的 sgRNA 活性预测方面实现了高精度，并且优于其他可用的计算机方法。此外， EpiCas-DL还可以识别影响sgRNA在基因沉默和激活中功效的表观遗传和序列特征，促进表观基因组编辑在研究和治疗中的应用。 EpiCas-DL可从 http://www.sunlab.fun:3838/EpiCas-DL 获取。