Maximizing Depth of PTM Coverage: Generating Robust MS Datasets for Computational Prediction Modeling

Post-translational modifications (PTMs) regulate complex biological processes through the modulation of protein activity, stability, and localization. Insights into the specific modification type and localization within a protein sequence can help ascertain functional significance. Computational models are increasingly demonstrated to offer a low-cost, high-throughput method for comprehensive PTM predictions. Algorithms are optimized using existing experimental PTM data, thus accurate prediction performance relies on the creation of robust datasets. Herein, advancements in mass spectrometry-based proteomics technologies to maximize PTM coverage are reviewed. Further, requisite experimental validation approaches for PTM predictions are explored to ensure that follow-up mechanistic studies are focused on accurate modification sites.