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Related Concept Videos

Proteomics01:33

Proteomics

7.2K
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
7.2K

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Updated: Jun 12, 2025

Large-scale Top-down Proteomics Using Capillary Zone Electrophoresis Tandem Mass Spectrometry
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Deep Profiling of Plasma Proteoforms with Engineered Nanoparticles for Top-Down Proteomics.

Che-Fan Huang1, Michael A Hollas1, Aniel Sanchez1

  • 1Proteomics Center of Excellence, Northwestern University, Evanston, Illinois 60208, United States.

Journal of Proteome Research
|September 23, 2024
PubMed
Summary

Nanoparticle enrichment dramatically increases proteome depth in human plasma. This method enables the detection of low-abundance proteins and proteoforms, advancing clinical proteomics for disease and aging research.

Keywords:
nanoparticlesplasmaprotein coronaproteoformstop-down proteomics

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Area of Science:

  • Proteomics
  • Biochemistry
  • Nanotechnology

Background:

  • Human plasma proteome analysis faces dynamic range challenges, limiting detection of low-abundance proteins.
  • Existing methods struggle to identify proteins beyond highly abundant ones like albumin and immunoglobins.

Purpose of the Study:

  • To develop and validate a nanoparticle protein corona approach for enriching low-abundance proteins and proteoforms from human plasma.
  • To significantly increase the depth of proteome analysis for identifying novel biomarkers.

Main Methods:

  • Utilized a nanoparticle protein corona strategy for selective and reproducible enrichment of plasma proteins.
  • Employed top-down proteomics to quantify differential enrichment and detect proteoforms.
  • Analyzed 2841 proteoforms from 114 proteins to assess enrichment efficiency.

Main Results:

  • Achieved up to a 105-fold increase in proteome depth, detecting proteoforms from ~1 μg/mL down to ~10 pg/mL.
  • Identified medium and low-abundance proteoforms involved in immunity and cell signaling, expanding beyond abundant proteins.
  • Demonstrated reproducible enrichment, enhancing the applicability of proteoform research.

Conclusions:

  • Nanoparticle enrichment overcomes dynamic range limitations in human plasma proteomics.
  • This approach enables deeper proteoform sequencing, crucial for clinical proteomics in disease and aging studies.
  • Opens new avenues for biomarker discovery by uncovering previously undetectable proteoforms.