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bioRxiv · 10.1101/2021.12.02.470943

CRSIPR-A-I: A webtool for the efficacy prediction of CRISPR activation and interference

Zheng, X.·Cui, J.·Wang, Y.·Zhang, J.·Wang, C.
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Abstract

AO_SCPLOWBSTRACTC_SCPLOWCRISPR-based gene activation (CRISPRa) or interference (CRISPRi) are powerful and easy-to-use approaches to modify the transcription of endogenous genes in eukaryotes. Successful CRISPRa/i requires sgRNA binding and alteration of local chromatin structure, hence largely depends on the original epigenetic status of the target. Consequently, the efficacy of the CRISPRa/i varies in a wide range when applied to target different gene loci, while a reliable prediction tool is unavailable. To address this problem, we integrated published single cell RNA-Seq data involved CRISPRa/i and epigenomic profiles from K562 cells, identified the significant epigenetic features contributing to CRISPRa/i efficacy by ranking the weight of each feature. We further established a mathematic model and built a user-friendly webtool to predict the CRISPRa/i efficacy of customer-designed sgRNA in different cells. Moreover, we experimentally validated our model by employing CROP-Seq assays. Our work provides both the epigenetic insights into CRISPRa/i and an effective tool for the users.

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Zheng, X., Cui, J., Wang, Y., Zhang, J., Wang, C.. 2021-12-03. CRSIPR-A-I: A webtool for the efficacy prediction of CRISPR activation and interference. https://doi.org/10.1101/2021.12.02.470943

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