A Comprehensive Evaluation of Large Language Models in Mining Gene Interactions and Pathway Knowledge.

ABSTRACT

Background: Understanding complex biological pathways, including gene-gene interactions and gene regulatory networks, is critical for exploring disease mechanisms and drug development. Manual literature curation of biological pathways is useful but cannot keep up with the exponential growth of the literature. Large-scale language models (LLMs), notable for their vast parameter sizes and comprehensive training on extensive text corpora, have great potential in automated text mining of biological pathways. Method: This study assesses the effectiveness of 21 LLMs, including both API-based models and open-source models. The evaluation focused on two key aspects gene regulatory relations (specifically, 'activation', 'inhibition', and 'phosphorylation') and KEGG pathway component recognition. The performance of these models was analyzed using statistical metrics such as precision, recall, F1 scores, and the Jaccard similarity index. Results: Our results indicated a significant disparity in model performance. Among the API-based models, ChatGPT-4 and Claude-Pro showed superior performance, with an F1 score of 0.4448 and 0.4386 for the gene regulatory relation prediction, and a Jaccard similarity index of 0.2778 and 0.2657 for the KEGG pathway prediction, respectively. Open-source models lagged their API-based counterparts, where Falcon-180b-chat and llama1-7b led with the highest performance in gene regulatory relations (F1 of 0.2787 and 0.1923, respectively) and KEGG pathway recognition (Jaccard similarity index of 0.2237 and 0. 2207, respectively). Conclusion: LLMs are valuable in biomedical research, especially in gene network analysis and pathway mapping. However, their effectiveness varies, necessitating careful model selection. This work also provided a case study and insight into using LLMs as knowledge graphs.