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Slice-PASEF: maximising ion utilisation in LC-MS proteomics

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Item Type:Preprint
Title:Slice-PASEF: maximising ion utilisation in LC-MS proteomics
Creators: Sinn, Ludwig R. ORCID logoORCID: https://orcid.org/0000-0003-4692-0681, Szyrwiel, Lukasz ORCID logoORCID: https://orcid.org/0000-0003-1983-2950, Grossmann, Justus, Lau, Kate, Faisst, Katharina, Qin, Di ORCID logoORCID: https://orcid.org/0000-0002-9730-4072, Mutschler, Florian ORCID logoORCID: https://orcid.org/0009-0002-0992-7171, Khoury, Luke ORCID logoORCID: https://orcid.org/0000-0001-7794-6812, Leduc, Andrew ORCID logoORCID: https://orcid.org/0000-0001-6234-0623, Ralser, Markus ORCID logoORCID: https://orcid.org/0000-0001-9535-7413, Coscia, Fabian ORCID logoORCID: https://orcid.org/0000-0002-2244-5081, Selbach, Matthias ORCID logoORCID: https://orcid.org/0000-0003-2454-8751, Slavov, Nikolai ORCID logoORCID: https://orcid.org/0000-0003-2035-1820, Nagaraj, Nagarjuna, Steger, Martin ORCID logoORCID: https://orcid.org/0000-0003-1637-8190 and Demichev, Vadim ORCID logoORCID: https://orcid.org/0000-0002-2424-9412
Abstract: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.
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2022.10.31.514544v3
Date:2 September 2025
Additional Information:The requested projects PXD063201, PXD063234, PXD063280 and PXD063371 are not public.
Official Publication:https://doi.org/10.1101/2022.10.31.514544
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