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Defining biologically grounded validation standards for deep learning-based post-translational modification (PTM) prediction
The CLASPP framework combines unsupervised sequence-space stratification with supervised contrastive learning in protein language model embedding space to predict 12 PTM types from a single model. Training and experimental validation were performed in humans, while out-of-distribution testing spanned diverse model organisms across the evolutionary tree shown. The model’s utility in phosphoproteomics workflows is demonstrated through the annotation of ubiquitination sites in the understudied DCLK3 kinase. By integrating evolutionary breadth, experimental validation, and behavioral testing, CLASPP establishes a framework for rigorous benchmarking of next-generation multi-PTM prediction models (Gravel et al., 2026).
Image Credit: Nathan Gravel, licensed under CC BY 4.0