Prediction of CRISPR On-Target Effects via Deep Learning

Condy Bao, Fuxiao Liu


Abstract
Since the advent of CRISPR-Cas9, a groundbreaking gene-editing technology that enables precise genomic modifications via a short RNA guide sequence, there has been a marked increase in the accessibility and application of this technology across various fields. The success of CRISPR-Cas9 has spurred further investment and led to the discovery of additional CRISPR systems, including CRISPR-Cas13. Distinct from Cas9, which targets DNA, Cas13 targets RNA, offering unique advantages for gene modulation. We focus on Cas13d, a variant known for its collateral activity where it non-specifically cleaves adjacent RNA molecules upon activation, a feature critical to its function. We introduce DeepFM-Crispr, a novel deep learning model developed to predict the on-target efficiency and evaluate the off-target effects of Cas13d. This model harnesses a large language model to generate comprehensive representations rich in evolutionary and structural data, thereby enhancing predictions of RNA secondary structures and overall sgRNA efficacy. A transformer-based architecture processes these inputs to produce a predictive efficacy score. Comparative experiments show that DeepFM-Crispr not only surpasses traditional models but also outperforms recent state-of-the-art deep learning methods in terms of prediction accuracy and reliability.
Anthology ID:
2024.nlp4science-1.2
Volume:
Proceedings of the 1st Workshop on NLP for Science (NLP4Science)
Month:
November
Year:
2024
Address:
Miami, FL, USA
Editors:
Lotem Peled-Cohen, Nitay Calderon, Shir Lissak, Roi Reichart
Venue:
NLP4Science
SIG:
Publisher:
Association for Computational Linguistics
Note:
Pages:
9–15
Language:
URL:
https://aclanthology.org/2024.nlp4science-1.2
DOI:
Bibkey:
Cite (ACL):
Condy Bao and Fuxiao Liu. 2024. Prediction of CRISPR On-Target Effects via Deep Learning. In Proceedings of the 1st Workshop on NLP for Science (NLP4Science), pages 9–15, Miami, FL, USA. Association for Computational Linguistics.
Cite (Informal):
Prediction of CRISPR On-Target Effects via Deep Learning (Bao & Liu, NLP4Science 2024)
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PDF:
https://aclanthology.org/2024.nlp4science-1.2.pdf