1. Introduction
CRISPR-mediated epigenome editing represents a cutting-edge technology that merges the precision targeting capabilities of the CRISPR-Cas system with the capacity to modify epigenetic marks on the genome. Epigenome editing technologies provides researchers with a novel approach to explore gene expression regulatory mechanisms, making it a hotspot in therapeutic, genetic and gene function researches. However, both CRISPR/Cas systems and epigenome editing systems can trigger off-target activities, posing challenges to their widespread application. To improve the editing efficiency and minimize the off-target effect, various epigenome editing systems have been developed and applied in different organisms and cell types. As a result, a great number of epigenome editing information has been published subsequently. However, the detailed information is discrete, making it a big challenge for researchers to obtain all current available data to evaluate the precision of different epigenome editing systems and design the optimal sgRNAs of target genes for further functional studies.
Herein, we developed CRISPRepi, a pioneering platform that consolidates extensive data from curated RNA-seq, ChIP-seq, Bisulfite-seq, and ATAC-seq datasets linked to 283 target genes manipulated by diverse epigenome editing methods across 6 species. It covers diverse cell types related to human diseases such as cancers as well as normal cells from published studies. It incorporats multiple annotations including “organisms”, “target gene”, “sgRNA sequences”, “sgRNA coordinate”, “strand direction”, “editing substrate”, “cell/tissue name”, “editing systems” and “cis-regulator element type”. CRISPRepi offers potential editing results from various epigenome editing systems like dCas9-Tet1, dCas9-KRAB, dCas9-LSD1, dCas9-p300, dCas9-SunTag-DNMT3A, and dCas9-VPR. Additionally, to assess off-target effects, we conduct a systematic analysis of gene expression profiles, presenting the fold change in gene expression before and after editing induced by CRISPR-based epigenome editing systems. Moreover, CRISPRepi incorporates tools for comparative analysis and visualization of epigenetic editing outcomes, enabling researchers to assess the efficacy and specificity of different editing strategies. Furthermore, users could search their own sgRNA sequences by inquiring the curated sgRNA sequences to infer the epigenome editing ability with appropriate epigenome systems.
2. Web interface of CRISPRepi
2.1 How to search CRISPRepi?
Users can search through two ways including 'quick search' and 'browse' as shown below.
2.2 Search Result
Search result including 'primary' and 'detail' sections as shown below.
2.3 Find datasets with sgRNA similar to yours
It would be helpful to infer newly designed sgRNA editing potentials with similar sgRNA sequence in editing systems. In order to facilitate users to evaluate the editing efficiency of their own designed sgRNA, we have integrated a similarity search tool into the database.
2.4 sgRNA efficiency prediction
We have developed a functional module for predicting sgRNA efficiency in CRISPepi. The efficiency of sgRNAs was predicted using the EpiCas-DL tool which is a deep learning-based framework specifically designed for predicting sgRNA activity in CRISPR-mediated epigenome editing.
