ArticlePLoS computational biology2015
A theoretical justification for single molecule peptide sequencing.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 82 citations in OpenAlex.
- Single-molecule peptide sequencing through reverse translation of peptides into DNA.Nature biotechnology · 2026Article
- Review
- Principles ofbioRxiv : the preprint server for biology · 2026Article
- Protein abundance inference via expectation-maximization in fluorosequencing.Bioinformatics advances · 2026Article
- Photolysis of the peptide bond at 193 and 222 nm.The Journal of chemical physics · 2025Article
- How Have Massively Parallel Sequencing Technologies Furthered Our Understanding of Oncogenesis and Cancer Progression?Methods in molecular biology (Clifton, N.J.) · 2025Review
- A generalized protein identification method for novel and diverse sequencing technologies.NAR genomics and bioinformatics · 2024Article
- Amplifiable protein identification via residue-resolved barcoding and composition code counting.National science review · 2024Article
- Estimating error rates for single molecule protein sequencing experiments.PLoS computational biology · 2024Article
- Full-length single-molecule protein fingerprinting.Nature nanotechnology · 2024Article
- Molecular sensitised probe for amino acid recognition within peptide sequences.Nature communications · 2023Article
- Beam search decoder for enhancing sequence decoding speed in single-molecule peptide sequencing data.PLoS computational biology · 2023Article
- Recent methodological advances towards single-cell proteomics.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2023Review
- Robust and scalable single-molecule protein sequencing with fluorosequencing.bioRxiv : the preprint server for biology · 2023Article
- Single-molecule fluorescence methods for protein biomarker analysis.Analytical and bioanalytical chemistry · 2023Review
- Amino acid sequence assignment from single molecule peptide sequencing data using a two-stage classifier.PLoS computational biology · 2023Article
- Sampling the proteome by emerging single-molecule and mass spectrometry methods.Nature methods · 2023Article
- Purification and characterization of novel isoforms of the polyphenol oxidase from Malus domestica fruit pulp.PloS one · 2023Article
- Evaluating the Effect of Dye-Dye Interactions of Xanthene-Based Fluorophores in the Fluorosequencing of Peptides.Bioconjugate chemistry · 2022Article
- Protein Sequencing, One Molecule at a Time.Annual review of biophysics · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The proteomes of cells, tissues, and organisms reflect active cellular processes and change continuously in response to intracellular and extracellular cues. Deep, quantitative profiling of the proteome, especially if combined with mRNA and metabolite measurements, should provide an unprecedented view of cell state, better revealing functions and interactions of cell components. Molecular diagnostics and biomarker discovery should benefit particularly from the accurate quantification of proteomes, since complex diseases like cancer change protein abundances and modifications. Currently, shotgun mass spectrometry is the primary technology for high-throughput protein identification and quantification; while powerful, it lacks high sensitivity and coverage. We draw parallels with next-generation DNA sequencing and propose a strategy, termed fluorosequencing, for sequencing peptides in a complex protein sample at the level of single molecules. In the proposed approach, millions of individual fluorescently labeled peptides are visualized in parallel, monitoring changing patterns of fluorescence intensity as N-terminal amino acids are sequentially removed, and using the resulting fluorescence signatures (fluorosequences) to uniquely identify individual peptides. We introduce a theoretical foundation for fluorosequencing and, by using Monte Carlo computer simulations, we explore its feasibility, anticipate the most likely experimental errors, quantify their potential impact, and discuss the broad potential utility offered by a high-throughput peptide sequencing technology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.