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The Next Generation of Protein Sequencing and Analysis Methods
Kingsley L-J Wong1,2, Mattias Tolhurst1,2, Oren A Fox1
1Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, Washington, USA;
Annual Review of Analytical Chemistry (Palo Alto, Calif.)
|February 23, 2026
Summary
New protein sequencing technologies promise to revolutionize proteomics by linking sequence, structure, and function. These innovations accelerate biological discovery and biomedical innovation, overcoming current challenges in protein analysis.
Area of Science:
- Proteomics
- Biotechnology
- Molecular Biology
Background:
- Proteomics faces challenges due to protein complexity, amplification difficulties, and diverse proteoforms.
- Current large-scale proteomics studies primarily rely on mass spectrometry.
- Existing methods struggle to comprehensively link protein sequence, structure, and function at scale.
Purpose of the Study:
- To review emerging protein sequencing and analysis technologies.
- To evaluate the mechanisms, progress, and challenges of novel proteomic techniques.
- To highlight innovations converging towards next-generation proteomic platforms.
Main Methods:
- Review of fluorosequencing, single-molecule sequencing, digital proteomics mapping, and nanopore-based protein sequencing.
- Analysis of technological mechanisms and current developmental stages.
- Assessment of commercial readiness and future potential.
Main Results:
- Several new technologies offer de novo, single-molecule, and higher-throughput protein sequencing.
- Fluorosequencing, single-molecule sequencing, digital proteomics mapping, and nanopore sequencing are nearing commercial implementation.
- These advancements promise to overcome limitations of current proteomic approaches.
Conclusions:
- Advances in protein sequencing are set to transform proteomics.
- These technologies will accelerate biological discovery and biomedical innovation.
- The convergence of innovations heralds a new era in proteomic analysis.
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