SubmissionNumber#=%=#61 FinalPaperTitle#=%=#Virtual CRISPR: Can LLMs Predict CRISPR Screen Results? ShortPaperTitle#=%=# NumberOfPages#=%=#11 CopyrightSigned#=%=#Steven Song JobTitle#==# Organization#==# 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. Author{1}{Firstname}#=%=#Steven Author{1}{Lastname}#=%=#Song Author{1}{Username}#=%=#songs1 Author{1}{Email}#=%=#songs1@uchicago.edu Author{1}{Affiliation}#=%=#University of Chicago Author{2}{Firstname}#=%=#Abdalla Author{2}{Lastname}#=%=#Abdrabou Author{2}{Email}#=%=#abdalla.abdrabou@northwestern.edu Author{2}{Affiliation}#=%=#Chan Zuckerberg Biohub Chicago Author{3}{Firstname}#=%=#Asmita Author{3}{Lastname}#=%=#Dabholkar Author{3}{Email}#=%=#asmita.edu.re@gmail.com Author{3}{Affiliation}#=%=#University of Illinois Urbana-Champaign Author{4}{Firstname}#=%=#Kastan Author{4}{Lastname}#=%=#Day Author{4}{Email}#=%=#kastanday@gmail.com Author{4}{Affiliation}#=%=#University of Illinois Urbana-Champaign Author{5}{Firstname}#=%=#Pavan Author{5}{Lastname}#=%=#Dharmoju Author{5}{Email}#=%=#Pavan.Dharmoju@northwestern.edu Author{5}{Affiliation}#=%=#Northwestern University Author{6}{Firstname}#=%=#Jason Author{6}{Lastname}#=%=#Perera Author{6}{Email}#=%=#jperera@uchicago.edu Author{6}{Affiliation}#=%=#Chan Zuckerberg Biohub Chicago Author{7}{Firstname}#=%=#Volodymyr Author{7}{Lastname}#=%=#Kindratenko Author{7}{Email}#=%=#kindrtnk@illinois.edu Author{7}{Affiliation}#=%=#University of Illinois Urbana-Champaign Author{8}{Firstname}#=%=#Aly A. Author{8}{Lastname}#=%=#Khan Author{8}{Email}#=%=#aakhan@uchicago.edu Author{8}{Affiliation}#=%=#University of Chicago ========== èéáğö