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Accelerating Drug Repurposing with AI: The Role of Large Language Models in Hypothesis Validation

Zunzunegui Sanz, I.; Otero-Carrasco, B.; Rodriguez-Gonzalez, A.

2025-06-20 bioinformatics
10.1101/2025.06.13.659527 bioRxiv
Show abstract

Drug repurposing accelerates drug discovery by identifying new therapeutic uses for existing drugs, but validating computational predictions remains a challenge. Large Language Models (LLMs) offer a potential solution by analyzing biomedical literature to assess drug-disease associations. This study evaluates four LLMs (GPT-4o, Claude-3, Gemini-2, and DeepSeek) using ten prompt strategies to validate repurposing hypotheses. The best-performing prompts and models were tested on 30 pathway-based cases and 10 benchmark cases. Results show that structured prompts enhance LLM accuracy, with GPT-4o and DeepSeek emerging as the most reliable models. Benchmark cases achieved significantly higher accuracy, precision, and F1-score (p < 0.001), while recall remained consistent across datasets. These findings highlight LLMs potential in drug repurposing validation while emphasizing the need for structured prompts and human oversight.

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