Single-cell proteomics enabled by next-generation sequencing or mass spectrometry
Abstract
In the last decade, single-cell RNA sequencing routinely performed on large numbers of single cells has greatly advanced our understanding of the underlying heterogeneity of complex biological systems. Technological advances have also enabled protein measurements, further contributing to the elucidation of cell types and states present in complex tissues. Recently, there have been independent advances in mass spectrometric techniques bringing us one step closer to characterizing single-cell proteomes. Here we discuss the challenges of detecting proteins in single cells by both mass spectrometry and sequencing-based methods. We review the state of the art for these techniques and propose that there is a space for technological advancements and complementary approaches that maximize the advantages of both classes of technologies.
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Mass spectrometry-based single-cell proteomics achieves a detection depth of about 1,500 to 2,500 proteins and is the most successful and extensively discussed in this review.
“Mass spectrometry-based single-cell proteomics (scMS), achieving a detection depth of about 1,500 ∼ 2,500 proteins, is the most successful and extensively discussed in this review [123].”
From Single-cell sequencing to multi-omics: technologies and applications (2024) · cites this paper as [123]
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Single-cell sequencing to multi-omics: technologies and applications
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“Furthermore, imaging-based approaches address the issue of spatial distribution [123].”
BackgroundMethodGraph neural networks for single-cell omics data: a review of approaches and applications
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“…a comprehensive view of cellular differentiation pattern, more precise methods such as single-cell technologies (transcriptomics or proteomics) 38,39 and spatiotemporal single-cell tracking 40,41 would further elucidate the detailed cellular composition and 3D organization during iHLO…”
- Authors
- Bennett, H. M., Stephenson, W., Rose, C. M., & Darmanis, S.
- Affiliations
- Genentech (US)
- Corresponding author
- Darmanis, Spyros
- Venue
- Nature Methods
- Published
- 2023-03
- Volume
- 20
- Issue
- 3
- Pages
- 363-374
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W4322766901
- Cited by
- 351
- References
- 126
- Citations by year
- 2026: 73 · 2025: 132 · 2024: 109 · 2023: 36 · 2022: 1
- FWCI
- 10.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- single-cell proteomics, single-cell mass spectrometry, single-cell RNA sequencing, cell type annotation, single-cell sequencing
- MeSH terms
- Mass Spectrometry, Proteome, Proteomics, High-Throughput Nucleotide Sequencing
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