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Related Concept Videos

Proteomics01:33

Proteomics

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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...
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Simultaneous In-Depth Single-Cell Proteomic and Metabolomic Analysis.

Jie Wu1,2, Fang-Hua Lu3, Li-Ye Tao2

  • 1Single-cell Proteomics Research Center, iChemFoundry platform and Institute for Intelligent Bio/Chem Manufacturing (iBCM), ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311200, China.

Analytical Chemistry
|April 27, 2026
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Summary
This summary is machine-generated.

This study introduces a novel hybrid-mode single-cell proteome and metabolome analysis (hybrid-scPMA) strategy. It enables deep dual-omics profiling in single cells, advancing cellular heterogeneity and disease mechanism research.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Analytical Chemistry

Background:

  • Simultaneous proteomic and metabolomic profiling at the single-cell level is essential for understanding cellular heterogeneity and disease mechanisms.
  • Achieving high-depth dual-omics analysis in the same single cell remains a significant technical challenge.
  • Existing methods often lack the depth or integration required for comprehensive single-cell multi-omics.

Purpose of the Study:

  • To develop a unified strategy for one-shot hybrid-mode single-cell proteome and metabolome analysis (hybrid-scPMA).
  • To establish an improved workflow integrating automated capture, simplified pretreatment, and hybrid-mode mass spectrometry detection.
  • To enable deep proteomic and metabolomic profiling in individual cells for enhanced biological insights.

Main Methods:

  • Utilized a hybrid-mode mass spectrometry (MS) approach combining data-independent acquisition (DIA) for proteomics and data-dependent acquisition (DDA) for metabolomics within a single liquid chromatography-mass spectrometry (LC-MS) run.
  • Developed an integrated workflow featuring automated single-cell capture, streamlined sample preparation, and LC separation.
  • Employed DIA-DDA hybrid-mode MS detection for simultaneous proteomic and metabolomic analysis.

Main Results:

  • Achieved an average identification of 3510 protein groups and 255 metabolites per single HepG2 cell, significantly increasing depth compared to previous methods.
  • Demonstrated time-resolved proteomic and metabolomic profiling of HepG2 single cells under sorafenib treatment.
  • Resolved drug response characteristics at the single-cell level, offering multi-omics insights into drug mechanisms.

Conclusions:

  • The proposed hybrid-scPMA strategy and workflow enable unprecedented depth in single-cell proteo-metabolomic analysis.
  • This approach provides valuable multi-omics insights into cellular responses to drug interventions at the single-cell level.
  • Hybrid-scPMA is a powerful tool for deciphering cellular heterogeneity and elucidating complex disease mechanisms.