Virtual CRISPR: Can LLMs Predict CRISPR Screen Results?

Steven Song, Abdalla Abdrabou, Asmita Dabholkar, Kastan Day, Pavan Dharmoju, Jason Perera, Volodymyr Kindratenko, Aly Khan


Abstract
CRISPR-Cas systems enable systematic investigation of gene function, but experimental CRISPR screens are resource-intensive. Here, we investigate the potential of Large Language Models (LLMs) to predict the outcomes of CRISPR screens in silico, thereby prioritizing experiments and accelerating biological discovery. We introduce a benchmark dataset derived from BioGRID-ORCS and manually curated sources, and evaluate the performance of several LLMs across various prompting strategies, including chain-of-thought and few-shot learning. Furthermore, we develop a novel, efficient prediction framework using LLM-derived embeddings, achieving significantly improved performance and scalability compared to direct prompting. Our results demonstrate the feasibility of using LLMs to guide CRISPR screen experiments.
Anthology ID:
2025.bionlp-1.30
Volume:
ACL 2025
Month:
August
Year:
2025
Address:
Viena, Austria
Editors:
Dina Demner-Fushman, Sophia Ananiadou, Makoto Miwa, Junichi Tsujii
Venues:
BioNLP | WS
SIG:
Publisher:
Association for Computational Linguistics
Note:
Pages:
354–364
Language:
URL:
https://preview.aclanthology.org/acl25-workshop-ingestion/2025.bionlp-1.30/
DOI:
Bibkey:
Cite (ACL):
Steven Song, Abdalla Abdrabou, Asmita Dabholkar, Kastan Day, Pavan Dharmoju, Jason Perera, Volodymyr Kindratenko, and Aly Khan. 2025. Virtual CRISPR: Can LLMs Predict CRISPR Screen Results?. In ACL 2025, pages 354–364, Viena, Austria. Association for Computational Linguistics.
Cite (Informal):
Virtual CRISPR: Can LLMs Predict CRISPR Screen Results? (Song et al., BioNLP 2025)
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PDF:
https://preview.aclanthology.org/acl25-workshop-ingestion/2025.bionlp-1.30.pdf
Supplementarymaterial:
 2025.bionlp-1.30.SupplementaryMaterial.zip
Supplementarymaterial:
 2025.bionlp-1.30.SupplementaryMaterial.txt