Single-cell protein analysis by mass spectrometry
Open accessAbstract
Human physiology and pathology arise from the coordinated interactions of diverse single cells. However, analyzing single cells has been limited by the low sensitivity and throughput of analytical methods. DNA sequencing has recently made such analysis feasible for nucleic acids but single-cell protein analysis remains limited. Mass spectrometry is the most powerful method for protein analysis, but its application to single cells faces three major challenges: efficiently delivering proteins/peptides to mass spectrometry detectors, identifying their sequences, and scaling the analysis to many thousands of single cells. These challenges have motivated corresponding solutions, including SCoPE design multiplexing and clean, automated, and miniaturized sample preparation. Synergistically applied, these solutions enable quantifying thousands of proteins across many single cells and establish a solid foundation for further advances. Building upon this foundation, the SCoPE concept will enable analyzing subcellular organelles and posttranslational modifications, while increases in multiplexing capabilities will increase the throughput and decrease cost.
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Single-cell and spatial proteomics have enabled the identification of protein expression changes in specific cell types and anatomical regions.
“Most proteomic studies rely on bulk samples, but recent innovations in single-cell and spatial proteomics have enabled the identification of protein expression changes in specific cell types and anatomical regions.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [180]
The Introduction (page not provided) explains that bulk proteomics averages out differences among cell types, while single-cell protein measurements can reveal them. The paper supports the single-cell portion of the claim, but the passages do not establish that spatial proteomics identifies protein-expression changes in specific anatomical regions. (LLM, conf=0.87)
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- Authors
- Slavov, N.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Slavov, Nikolai
- ORCID
- Slavov, Nikolai
- Venue
- Current Opinion in Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 60
- Pages
- 1-9
- ISSN
- 1367-5931 (ISSN-L)
- PMC
- PMC7767890
- OpenAlex
- W3035881786
- Cited by
- 164
- References
- 2
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 26 · 2023: 36 · 2022: 27 · 2021: 29 · 2020: 6 · 2019: 1
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Funders
- Chan Zuckerberg Initiative
- Merck Sharp and Dohme
- National Institute of General Medical Sciences
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- single-cell proteomics, mass spectrometry, sample preparation, protein quantification, multiplexing, subcellular organelles, post-translational modification
- MeSH terms
- Animals, Humans, Proteins, Mass Spectrometry, Single-Cell Analysis
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