The biological activity of a protein is regulated at many levels ranging from control of transcription and translation to post-translational modifications (PTM). Proteolytic processing is an irreversible PTM generating novel isoforms of a mature protein termed proteoforms. Proteoform dynamics is a major focus of current proteome research, since it has been associated with many pathological conditions. Mass-spectrometry (MS)-based proteomics and PTM-specific enrichment workflows have become the methods of choice to study proteoforms in vitro and in vivo. Here, we give an overview of currently available MS-based degradomics methods and outline how they can be optimally applied to study protease cleavage events. We discuss the advantages and disadvantages of selected approaches and describe state-of-the-art improvements in degradomics technologies. By introducing the concept of combinatorial degradomics, a combination of global discovery degradomics and highly sensitive targeted degradomics, we demonstrate how MS-based degradomics further evolves as a powerful tool in biomedical protease research.

中文翻译：

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组合降解组学：揭示生物系统中蛋白水解过程的精密工具。

蛋白质的生物学活性受到许多水平的调节，范围从转录和翻译控制到翻译后修饰（PTM）。蛋白水解过程是不可逆的PTM，它产生称为蛋白形式的成熟蛋白的新型同工型。蛋白质组动力学是当前蛋白质组学研究的主要重点，因为它已与许多病理状况相关联。基于质谱（MS）的蛋白质组学和特定于PTM的富集工作流程已成为在体外和体内研究蛋白形式的选择方法。在这里，我们概述了当前可用的基于MS的降解组学方法，并概述了如何将它们最佳地用于研究蛋白酶裂解事件。我们讨论了所选方法的优缺点，并描述了降解组学技术的最新发展。