PTMNavigator: Interactive Visualization of Differentially Regulated Post-Translational Modifications in Cellular Signaling Pathways

Abstract

AbstractPost-translational modifications (PTMs) play a governing role in regulating cellular signaling, fine-tuning protein function, and orchestrating complex biological processes. Despite their importance, the lack of comprehensive tools for studying PTMs from a pathway-centric perspective has limited our ability to understand how PTMs modulate cellular pathways on a molecular level. Here, we present PTMNavigator, a tool integrated into the ProteomicsDB platform, which offers an interactive interface for researchers to overlay experimental PTM data on top of ∼3000 well-curated pathway diagrams. This offers a comprehensive view of the intricate relationship between PTMs and signaling pathways. To demonstrate the utility of PTMNavigator, we applied it to two phosphoproteomics perturbation datasets. First, PTMNavigator enhanced pathway enrichment analysis by showing how the regulated peptides are distributed in the pathways with high enrichment scores. Second, it visualized how drug treatments result in a discernable flow of PTM-driven signaling within pathways. Third, PTMNavigator aided in extending existing pathways by uncovering previously unknown relationships between PTMs and pathway components. By facilitating the discovery of novel PTM-pathway interactions and enhancing our understanding of cellular signaling dynamics, PTMNavigator advances our knowledge of PTM biology and its implications in health and disease.