Peking University Researchers Quantify Essentiality of 617,462 Human Microproteins Using AI
A novel deep learning model, developed bya Peking University team and published in a Nature portfolio journal, leverages a pre-trained large language model to predict and quantify the essentiality of human proteins,significantly advancing our understanding of human biology and disease.
The identification of human essential proteins (HEPs), crucial for survival and development, has traditionally relied on expensiveand time-consuming experimental methods. Existing computational approaches have limitations, primarily focusing on cell line-level predictions, which often fail to reflect the complexities of HEPs in living humans and animal models. This disparity highlights a critical gap inour understanding of protein function and its implications for human health.
To address this challenge, researchers at Peking University developed the Protein Importance Calculator (PIC), a sequence-based deep learning model. PIC utilizes a fine-tuned pre-trainedprotein language model, offering a significant leap forward in accuracy and scope compared to existing methods. Crucially, PIC provides comprehensive predictions across three distinct levels: human, cell lines, and mice, offering a more holistic and nuanced perspective on protein essentiality.
The researchers defined a protein essentiality score derived from PIC,enabling the quantification of the essentiality of individual proteins. This score’s validity was rigorously tested through a series of biological analyses. Furthermore, the team demonstrated the biomedical value of this score by identifying potential prognostic biomarkers for breast cancer and, most significantly, quantifying the essentiality of an unprecedented 617,462 human microproteins. This represents a massive expansion of our knowledge base concerning the human proteome.
The study, titled Comprehensive prediction and analysis of human protein essentiality based on a pretrained large language model, published on November 27, 2024, in a Nature portfoliojournal, underscores the transformative potential of AI in biological research. The development of PIC not only streamlines the identification of essential proteins but also provides a powerful tool for investigating disease mechanisms and developing novel therapeutic strategies. The ability to quantify the essentiality of such a vast number of microproteins opens up exciting new avenues forresearch into the intricate workings of the human body and the development of personalized medicine. Future research could focus on expanding the application of PIC to other organisms and exploring its potential in drug discovery and development.
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