Top-down mass spectrometry (MS) analyzes intact proteins at the proteoform level, which allows researchers to better understand the functions of protein modifications. Recently, top-down proteomics has increased in popularity due to advancements in high-resolution mass spectrometers, increased efficiency in liquid chromatography (LC) separation, and advances in data analysis software. Some unique protein proteoforms, which have been distinguished using top-down MS, have even been shown to exhibit marked variation in biological function compared to similar proteoforms. However, the qualitative identification of a particular proteoform may not be enough to determine the biological relevance of that proteoform. Quantitative top-down MS methods have been notably applied to the study of the differing biological functions of protein proteoforms and have allowed researchers to explore proteomes at the proteoform, rather than the peptide, level. Here, we review the top-down MS methods that have been used to quantitatively identify intact proteins, discuss current applications of quantitative top-down MS analysis, and present new areas where quantitative top-down MS analysis may be implemented.

中文翻译：

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高通量定量自上而下的蛋白质组学。

自顶向下质谱（MS）在蛋白形式水平上分析完整的蛋白质，这使研究人员可以更好地了解蛋白质修饰的功能。近来，由于高分辨率质谱仪的进步，液相色谱（LC）分离效率的提高以及数据分析软件的进步，自上而下的蛋白质组学已变得越来越流行。使用自上而下的MS进行了区分的一些独特的蛋白质蛋白形式，甚至被证明与相似的蛋白形式相比，在生物学功能上表现出明显的变化。但是，对特定蛋白形式的定性鉴定可能不足以确定该蛋白形式的生物学相关性。自上而下的定量质谱分析方法已特别应用于蛋白质蛋白形式的不同生物学功能的研究，并使研究人员能够在蛋白形式而不是肽水平上探索蛋白质组。在这里，我们回顾了用于定量鉴定完整蛋白质的自上而下的MS方法，讨论了自上而下的定量MS分析的当前应用，并介绍了可实施自上​​而下的定量MS分析的新领域。