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KAIST Proposes AI-Driven Strategy to Solve Long-Standing Mystery of Gene Function
<(From Left) Distinguisehd Professor Sang Yup Lee, Dr. Gi Bae Kim, Professor Bernhard O. Palsson> “We know the genes, but not their functions.” To resolve this long-standing bottleneck in microbial research, a joint research team has proposed a cutting-edge research strategy that leverages Artificial Intelligence (AI) to drastically accelerate the discovery of microbial gene functions. KAIST announced on January 12th that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering, in collaboration with Professor Bernhard Palsson from the Department of Bioengineering at UCSD, has published a comprehensive review paper. The study systematically analyzes and organizes the latest AI-based research approaches aimed at revolutionizing the speed of gene function discovery. Since the early 2000s, when whole-genome sequencing became a reality, there were high expectations that the genetic blueprint of life would be fully decoded. However, even twenty years later, the roles of a significant portion of genes within microbial genomes remain unknown. While various experimental methods—such as gene deletion, analysis of gene expression profiles, and in vitro activity assays—have been employed, discovering gene functions remains a time-consuming and costly endeavor. This is primarily due to the limitations of large-scale experimentation, complex biological interactions, and the discrepancy between laboratory results and actual in vivo responses. To overcome these hurdles, the research team emphasized that an AI-driven approach combining computational biology with experimental biology is essential. In this paper, the team provides a comprehensive overview of computational biology approaches that have facilitated gene function discovery, ranging from traditional sequence similarity analysis to the latest deep-learning-based AI models. Notably, 3D protein structure prediction technologies such as AlphaFold (developed by Google DeepMind) and RoseTTAFold (developed by the University of Washington) have opened new doors. These tools go beyond simple functional estimation, offering the potential to understand the underlying mechanisms of how gene functions operate. Furthermore, generative AI is now extending research boundaries toward designing proteins with specifically desired functions. Focusing on transcription factors (proteins that act as genetic switches) and enzymes (proteins that catalyze chemical reactions), the team presented various application cases and future research directions that integrate gene sequence analysis, protein structure prediction, and diverse metagenomic analyses. <Schematic illustration of computational biology methods for enzyme function prediction>
2026.01.12
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