Müller Julian, Bayer Florian P, Wilhelm Mathias, Schuh Maximilian G, Kuster Bernhard, The Matthew
Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Freising, Germany.
Computational Mass Spectrometry, School of Life Sciences, Technical University of Munich, Freising, Germany.
Nat Commun. 2025 Jan 8;16(1):510. doi: 10.1038/s41467-024-55533-y.
Post-translational modifications (PTMs) play pivotal roles 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 that offers an interactive interface for researchers to overlay experimental PTM data with pathway diagrams. PTMNavigator provides ~3000 canonical pathways from manually curated databases, enabling users to modify and create custom diagrams tailored to their data. Additionally, PTMNavigator automatically runs kinase and pathway enrichment algorithms whose results are directly integrated into the visualization. This offers a comprehensive view of the intricate relationship between PTMs and signaling pathways. We demonstrate the utility of PTMNavigator by applying it to two phosphoproteomics datasets, showing how it can enhance pathway enrichment analysis, visualize how drug treatments result in a discernable flow of PTM-driven signaling, and aid in proposing extensions to existing pathways. By enhancing our understanding of cellular signaling dynamics and facilitating the discovery of PTM-pathway interactions, PTMNavigator advances our knowledge of PTM biology and its implications in health and disease.
翻译后修饰(PTMs)在调节细胞信号传导、微调蛋白质功能以及协调复杂的生物学过程中发挥着关键作用。尽管它们很重要,但缺乏从以通路为中心的角度研究PTMs的综合工具,限制了我们在分子水平上理解PTMs如何调节细胞通路的能力。在这里,我们展示了PTMNavigator,这是一种集成到ProteomicsDB平台中的工具,它为研究人员提供了一个交互式界面,以便将实验性PTM数据与通路图叠加。PTMNavigator从人工策划的数据库中提供约3000条规范通路,使用户能够修改和创建适合其数据的自定义图。此外,PTMNavigator会自动运行激酶和通路富集算法,其结果会直接整合到可视化中。这提供了PTMs与信号通路之间复杂关系的全面视图。我们通过将PTMNavigator应用于两个磷酸蛋白质组学数据集来证明其效用,展示了它如何增强通路富集分析、可视化药物治疗如何导致PTM驱动的信号传导的可辨别流程,以及有助于提出对现有通路的扩展。通过增强我们对细胞信号传导动力学的理解并促进PTM-通路相互作用的发现,PTMNavigator推进了我们对PTM生物学及其在健康和疾病中的影响的认识。