Sinn Ludwig R, Szyrwiel Lukasz, Grossmann Justus, Lau Kate, Faisst Katharina, Qin Di, Mutschler Florian, Khoury Luke, Leduc Andrew, Ralser Markus, Coscia Fabian, Selbach Matthias, Slavov Nikolai, Nagaraj Nagarjuna, Steger Martin, Demichev Vadim
Department of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Spatial Proteomics Group, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
bioRxiv. 2025 Sep 2:2022.10.31.514544. doi: 10.1101/2022.10.31.514544.
Quantitative mass spectrometry (MS)-based proteomics has become a streamlined technology with a wide range of usage. Many emerging applications, such as single-cell proteomics, spatial proteomics of tissue sections and the profiling of low-abundant posttranslational modifications, require the analysis of minimal sample amounts and are thus constrained by the sensitivity of the workflow. Here, we present Slice-PASEF, a mass spectrometry technology that leverages trapped ion mobility separation of ions to attain the theoretical maximum of tandem MS sensitivity. We implement Slice-PASEF using a new module in our DIA-NN software and show that Slice-PASEF uniquely enables precise quantitative proteomics of low sample amounts. We further demonstrate its utility towards a range of applications, including single cell proteomics and degrader drug screens via ubiquitinomics.
基于定量质谱（MS）的蛋白质组学已成为一种具有广泛用途的简化技术。许多新兴应用，如单细胞蛋白质组学、组织切片的空间蛋白质组学以及低丰度翻译后修饰的分析，都需要对极少量样本进行分析，因此受到工作流程灵敏度的限制。在此，我们介绍Slice-PASEF，这是一种利用离子阱离子淌度分离来实现串联质谱灵敏度理论最大值的质谱技术。我们在DIA-NN软件中使用一个新模块实现了Slice-PASEF，并表明Slice-PASEF能够独特地实现对少量样本的精确蛋白质组定量分析。我们进一步证明了它在一系列应用中的效用，包括单细胞蛋白质组学和通过泛素组学进行的降解剂药物筛选。
