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

Author

Listed:
  • 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
    University of Wisconsin—Madison)

  • Bifan Chen

    (University of Wisconsin—Madison)

  • Zhijie Wu

    (University of Wisconsin—Madison)

  • Stanford D. Mitchell

    (University of Wisconsin—Madison
    University of Wisconsin—Madison)

  • Tania M. Guardado-Alvarez

    (University of Wisconsin—Madison)

  • Song Jin

    (University of Wisconsin—Madison)

  • Ying Ge

    (University of Wisconsin—Madison
    University of Wisconsin—Madison
    University of Wisconsin—Madison)

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.

Suggested Citation

  • Timothy N. Tiambeng & David S. Roberts & Kyle A. Brown & Yanlong Zhu & Bifan Chen & Zhijie Wu & Stanford D. Mitchell & Tania M. Guardado-Alvarez & Song Jin & Ying Ge, 2020. "Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17643-1
    DOI: 10.1038/s41467-020-17643-1
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    Cited by:

    1. Emily A. Chapman & David S. Roberts & Timothy N. Tiambeng & Jãán Andrews & Man-Di Wang & Emily A. Reasoner & Jake A. Melby & Brad H. Li & Donguk Kim & Andrew J. Alpert & Song Jin & Ying Ge, 2023. "Structure and dynamics of endogenous cardiac troponin complex in human heart tissue captured by native nanoproteomics," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Xinyang Shao & Meng Tian & Junlong Yin & Haifeng Duan & Ye Tian & Hui Wang & Changsheng Xia & Ziwei Wang & Yanxi Zhu & Yifan Wang & Lingxiao Chaihu & Minjie Tan & Hongwei Wang & Yanyi Huang & Jianbin , 2024. "Biofunctionalized dissolvable hydrogel microbeads enable efficient characterization of native protein complexes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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