功能蛋白质组的复杂性远远超出编码基因组，导致出现数百万个蛋白质型。研究蛋白质型及其功能角色对于了解细胞生理学及其在疾病中的失调非常重要，但是系统性地进行很有挑战性。在这里，我们应用具有深度肽覆盖的热力蛋白质组学技术，检测不同细胞遗传异常的急性淋巴细胞白血病细胞系中的功能蛋白质组群。我们检测到15,846个蛋白质型，捕获来自9,290个基因的不同剪切、裂解和翻译后修饰的蛋白质。我们确定了蛋白质型对的差异性共聚和它们与疾病生物学之间的联系。此外，我们系统性地利用测量的生物物理蛋白质型状态来寻找特定的药物敏感性生物标志物。因此，我们的方法为系统检测和功能注释蛋白质组群提供了一个强大而独特的工具。 ©2023作者。

The complexity of the functional proteome extends considerably beyond the coding genome, resulting in millions of proteoforms. Investigation of proteoforms and their functional roles is important to understand cellular physiology and its deregulation in diseases but challenging to perform systematically. Here we applied thermal proteome profiling with deep peptide coverage to detect functional proteoform groups in acute lymphoblastic leukemia cell lines with different cytogenetic aberrations. We detected 15,846 proteoforms, capturing differently spliced, cleaved and post-translationally modified proteins expressed from 9,290 genes. We identified differential co-aggregation of proteoform pairs and established links to disease biology. Moreover, we systematically made use of measured biophysical proteoform states to find specific biomarkers of drug sensitivity. Our approach, thus, provides a powerful and unique tool for systematic detection and functional annotation of proteoform groups.© 2023. The Author(s).