Ultra-fast proteomics with Scanning SWATH
Journal article, 2021
Accurate quantification of the proteome remains challenging for large sample series and longitudinal experiments. We report a data-independent acquisition method, Scanning SWATH, that accelerates mass spectrometric (MS) duty cycles, yielding quantitative proteomes in combination with short gradients and high-flow (800 µl min ) chromatography. Exploiting a continuous movement of the precursor isolation window to assign precursor masses to tandem mass spectrometry (MS/MS) fragment traces, Scanning SWATH increases precursor identifications by ~70% compared to conventional data-independent acquisition (DIA) methods on 0.5–5-min chromatographic gradients. We demonstrate the application of ultra-fast proteomics in drug mode-of-action screening and plasma proteomics. Scanning SWATH proteomes capture the mode of action of fungistatic azoles and statins. Moreover, we confirm 43 and identify 11 new plasma proteome biomarkers of COVID-19 severity, advancing patient classification and biomarker discovery. Thus, our results demonstrate a substantial acceleration and increased depth in fast proteomic experiments that facilitate proteomic drug screens and clinical studies. –1
Author
Christoph B. Messner
Charité University Medicine Berlin
The Francis Crick Institute
Vadim Demichev
The Francis Crick Institute
University of Cambridge
Charité University Medicine Berlin
Nic Bloomfield
MDS SCIEX
Jason S.L. Yu
The Francis Crick Institute
Matthew White
The Francis Crick Institute
Marco Kreidl
The Francis Crick Institute
Anna Sophia Egger
The Francis Crick Institute
Anja Freiwald
Charité University Medicine Berlin
Gordana Ivosev
MDS SCIEX
Fras Wasim
MDS SCIEX
Aleksej Zelezniak
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
The Francis Crick Institute
Linda Jürgens
Charité University Medicine Berlin
Norbert Suttorp
Charité University Medicine Berlin
Leif Erik Sander
Charité University Medicine Berlin
Florian Kurth
Universitatsklinikum Hamburg-Eppendorf und Medizinische Fakultat
Charité University Medicine Berlin
Kathryn S. Lilley
University of Cambridge
Michael Mülleder
Charité University Medicine Berlin
Stephen Tate
MDS SCIEX
M. Ralser
Charité University Medicine Berlin
The Francis Crick Institute
Nature Biotechnology
1087-0156 (ISSN) 15461696 (eISSN)
Vol. 39 7 846-854Subject Categories
Pharmaceutical Sciences
Analytical Chemistry
Medical Image Processing
DOI
10.1038/s41587-021-00860-4
PubMed
33767396