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journal contribution
posted on 2024-02-01, 17:48authored byDijana Vitko, Wan-Fang Chou, Sara Nouri Golmaei, Joon-Yong Lee, Chinmay Belthangady, John Blume, Jessica K. Chan, Guillermo Flores-Campuzano, Yuntao Hu, Manway Liu, Mark A. Marispini, Megan G. Mora, Saividya Ramaswamy, Purva Ranjan, Preston B. Williams, Robert J. X. Zawada, Philip Ma, Bruce E. Wilcox
Mass spectrometry
(MS) is a valuable tool for plasma proteome profiling
and disease biomarker discovery. However, wide-ranging plasma protein
concentrations, along with technical and biological variabilities,
present significant challenges for deep and reproducible protein quantitation.
Here, we evaluated the qualitative and quantitative performance of
timsTOF HT and timsTOF Pro 2 mass spectrometers for analysis of neat
plasma samples (unfractionated) and plasma samples processed using
the Proteograph Product Suite (Proteograph) that enables robust deep
proteomics sampling prior to mass spectrometry. Samples were evaluated
across a wide range of peptide loading masses and liquid chromatography
(LC) gradients. We observed up to a 76% increase in total plasma peptide
precursors identified and a >2-fold boost in quantifiable plasma
peptide
precursors (CV < 20%) with timsTOF HT compared to Pro 2. Additionally,
approximately 4.5 fold more plasma peptide precursors were detected
by both timsTOF HT and timsTOF Pro 2 in the Proteograph analyzed plasma
vs neat plasma. In an exploratory analysis of 20 late-stage lung cancer
and 20 control plasma samples with the Proteograph, which were expected
to exhibit distinct proteomes, an approximate 50% increase in total
and statistically significant plasma peptide precursors (q < 0.05) was observed with timsTOF HT compared to Pro 2. Our data
demonstrate the superior performance of timsTOF HT for identifying
and quantifying differences between biologically diverse samples,
allowing for improved disease biomarker discovery in large cohort
studies. Moreover, researchers can leverage data sets from this study
to optimize their liquid chromatography–mass spectrometry (LC–MS)
workflows for plasma protein profiling and biomarker discovery. (ProteomeXchange
identifier: PXD047854 and PXD047839).