Bridging artificial intelligence and biological sciences: A comprehensive review of large language models in bioinformatics

Abstract

Large language models (LLMs), representing a breakthrough advancement in artificial intelligence, have demonstrated substantial application value and development potential in bioinformatics research, particularly showing significant progress in the processing and analysis of complex biological data. This comprehensive review systematically examines the development and applications of LLMs in bioinformatics, with particular emphasis on their advancements in protein and nucleic acid structure prediction, omics analysis, drug design and screening, and biomedical literature mining. This work highlights the distinctive capabilities of LLMs in end-to-end learning and knowledge transfer paradigms. Additionally, this paper thoroughly discusses the major challenges confronting LLMs in current applications, including key issues such as model interpretability and data bias. Furthermore, this review comprehensively explores the potential of LLMs in cross-modal learning and interdisciplinary development. In conclusion, this paper aims to systematically summarize the current research status of LLMs in bioinformatics, objectively evaluate their advantages and limitations, and provide insights and recommendations for future research directions, thereby positioning LLMs as essential tools in bioinformatics research and fostering innovative developments in the biomedical field.