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.

Recent advances in language modeling demonstrate the need for high-quality domain-specific training data, especially for tasks that require specialized knowledge. General-purpose models, while versatile, often lack the depth needed for expert-level tasks because of limited domain-specific information. Domain adaptation training can enhance these models, but it demands substantial, high-quality data. To address this, we propose ORBIT, a cost-efficient methodology for curating massive, high-quality domain-specific datasets from noisy web sources, tailored for training specialist large language models. Using astronomy as a primary case study, we refined the 1.3T-token FineWeb-Edu dataset into a high-quality, 10B-token subset focused on astronomy. Fine-tuning LLaMA-3-8B on a 1B-token astronomy subset improved performance on the MMLU astronomy benchmark from 69% to 76% and achieved top results on AstroBench, an astronomy-specific benchmark. Moreover, our model (Orbit-LLaMA) outperformed LLaMA-3-8B-base, with GPT-4o evaluations preferring it in 73% of cases across 1000 astronomy-specific questions. Additionally, we validated ORBIT’s generalizability by applying it to law and medicine, achieving a significant improvement of data quality compared to an unfiltered baseline. We open-source the ORBIT methodology, including the curated datasets, the codebase, and the resulting model.