1. Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum
- Author
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Song Jin, Ying Ge, Yanlong Zhu, Zhijie Wu, Stanford D. Mitchell, Kyle A. Brown, David S. Roberts, Tania M. Guardado-Alvarez, Bifan Chen, and Timothy N. Tiambeng
- Subjects
0301 basic medicine ,Proteomics ,Proteomics methods ,Cardiac troponin ,Proteome ,Science ,General Physics and Astronomy ,Serum Albumin, Human ,02 engineering and technology ,Computational biology ,Superparamagnetic nanoparticles ,General Biochemistry, Genetics and Molecular Biology ,Mass Spectrometry ,Article ,03 medical and health sciences ,Humans ,Nanotechnology ,lcsh:Science ,Magnetite Nanoparticles ,Multidisciplinary ,Chemistry ,Troponin I ,Reproducibility of Results ,General Chemistry ,Blood Proteins ,021001 nanoscience & nanotechnology ,Biomarker (cell) ,030104 developmental biology ,Cardiovascular diseases ,Post translational ,Protein processing ,Nanoparticles ,lcsh:Q ,0210 nano-technology ,Protein Processing, Post-Translational ,Biomarkers ,Blood Chemical Analysis - 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., Top-down proteomics can provide unique insights into the biological variations of protein biomarkers but detecting low-abundance proteins in body fluids remains challenging. Here, the authors develop a nanoparticle-based top-down proteomics approach enabling enrichment and detailed analysis of cardiac troponin I in human serum.
- Published
- 2020