Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum

Timothy N. Tiambeng, David S. Roberts, Kyle A. Brown, Yanlong Zhu, Bifan Chen, Zhijie Wu, Stanford D. Mitchell, Tania M. Guardado-Alvarez, Song Jin () and Ying Ge ()
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Timothy N. Tiambeng: University of Wisconsin—Madison
David S. Roberts: University of Wisconsin—Madison
Kyle A. Brown: University of Wisconsin—Madison
Yanlong Zhu: University of Wisconsin—Madison
Bifan Chen: University of Wisconsin—Madison
Zhijie Wu: University of Wisconsin—Madison
Stanford D. Mitchell: University of Wisconsin—Madison
Tania M. Guardado-Alvarez: University of Wisconsin—Madison
Song Jin: University of Wisconsin—Madison
Ying Ge: University of Wisconsin—Madison

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Top-down mass spectrometry (MS)-based proteomics provides a comprehensive analysis of proteoforms to achieve a proteome-wide understanding of protein functions. However, the MS detection of low-abundance proteins from blood remains an unsolved challenge due to the extraordinary dynamic range of the blood proteome. Here, we develop an integrated nanoproteomics method coupling peptide-functionalized superparamagnetic nanoparticles (NPs) with top-down MS for the enrichment and comprehensive analysis of cardiac troponin I (cTnI), a gold-standard cardiac biomarker, directly from serum. These NPs enable the sensitive enrichment of cTnI ( 1010 more abundant than cTnI). We demonstrate that top-down nanoproteomics can provide high-resolution proteoform-resolved molecular fingerprints of diverse cTnI proteoforms to establish proteoform-pathophysiology relationships. This scalable and reproducible antibody-free strategy can generally enable the proteoform-resolved analysis of low-abundance proteins directly from serum to reveal previously unachievable molecular details.

Date: 2020
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DOI: 10.1038/s41467-020-17643-1

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