Artificial Intelligence Uncovers Link Between Protein Modifications, Mutations, and Disease

Researchers at Baylor College of Medicine have introduced an innovative AI model, DeepMVP, that brings new understanding to how post-translational modifications (PTMs) of proteins connect genetic mutations with various diseases. Published in Nature Methods, this advanced computational tool significantly surpasses existing models, offering promising avenues for developing targeted therapies. Proteins perform essential roles in the body, from tissue growth to metabolic regulation and immune defense. Their functions are often influenced by PTMs—chemical modifications like phosphorylation or glycosylation that occur after protein synthesis. These modifications dictate a protein’s activity, location, stability, and interactions. When PTMs are abnormal or disrupted due to genetic mutations, they can lead to diseases such as cancer, cardiovascular conditions, and neurological disorders. Understanding where PTMs occur within proteins and how mutations affect these sites is crucial for predicting disease pathways. DeepMVP was trained using the PTMAtlas, a comprehensive database with nearly 400,000 PTM sites across human proteins. This resource was created by meticulous reanalysis of public datasets, enabling the model to recognize patterns in protein sequences associated with PTMs. The model excels in predicting PTM sites and assessing how mutations may alter these modifications. In testing, DeepMVP correctly identified PTM sites in 81% of known cases and accurately predicted the impact of mutations in 97% of instances, outperforming eight other similar tools. Its effectiveness extends to predicting effects in viral proteins, including SARS-CoV-2. The tool’s potential spans numerous fields, including cancer research, neurology, and drug development, expediting understanding of mutation-driven disease mechanisms. DeepMVP is freely accessible to researchers worldwide at deepmvp.ptmax.org, promising to accelerate discoveries and improve therapeutic strategies across various medical disciplines.