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Predicting CRISPR-Cas12a guide efficiency for targeting using machine learning

Author

Listed:
  • Aidan O’Brien
  • Denis C Bauer
  • Gaetan Burgio

Abstract

Genome editing through the development of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat)–Cas technology has revolutionized many fields in biology. Beyond Cas9 nucleases, Cas12a (formerly Cpf1) has emerged as a promising alternative to Cas9 for editing AT-rich genomes. Despite the promises, guide RNA efficiency prediction through computational tools search still lacks accuracy. Through a computational meta-analysis, here we report that Cas12a target and off-target cleavage behavior are a factor of nucleotide bias combined with nucleotide mismatches relative to the protospacer adjacent motif (PAM) site. These features helped to train a Random Forest machine learning model to improve the accuracy by at least 15% over existing algorithms to predict guide RNA efficiency for the Cas12a enzyme. Despite the progresses, our report underscores the need for more representative datasets and further benchmarking to reliably and accurately predict guide RNA efficiency and off-target effects for Cas12a enzymes.

Suggested Citation

  • Aidan O’Brien & Denis C Bauer & Gaetan Burgio, 2023. "Predicting CRISPR-Cas12a guide efficiency for targeting using machine learning," PLOS ONE, Public Library of Science, vol. 18(10), pages 1-22, October.
    • Handle: RePEc:plo:pone00:0292924
    DOI: 10.1371/journal.pone.0292924
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    References listed on IDEAS

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    1. Su Moon & Jeong Mi Lee & Jeong Gu Kang & Nan-Ee Lee & Dae-In Ha & Do Yon Kim & Sun Hee Kim & Kwangsun Yoo & Daesik Kim & Jeong-Heon Ko & Yong-Sam Kim, 2018. "Highly efficient genome editing by CRISPR-Cpf1 using CRISPR RNA with a uridinylate-rich 3′-overhang," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    2. Jintan Liu & Sanjana Srinivasan & Chieh-Yuan Li & I-Lin Ho & Johnathon Rose & MennatAllah Shaheen & Gang Wang & Wantong Yao & Angela Deem & Chris Bristow & Traver Hart & Giulio Draetta, 2019. "Pooled library screening with multiplexed Cpf1 library," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
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