Sequencing-Grade De novo Analysis of MS/MS Triplets (CID/HCD/ETD) From Overlapping Peptides
peer-reviewed · Journal of Proteome Research · 2013
| Date | 2013-06-07 |
| Type | peer-reviewed |
| Venue | Journal of Proteome Research |
| Publisher | American Chemical Society (ACS) |
| Contribution | algorithm |
| DOI | 10.1021/pr400173d |
| Citations (OpenAlex) | 73 |
| Venue 2-year citedness | 3.48 |
Abstract
Full-length de novo sequencing of unknown proteins remains a challenging open problem. Traditional methods that sequence spectra individually are limited by short peptide length, incomplete peptide fragmentation, and ambiguous de novo interpretations. We address these issues by determining consensus sequences for assembled tandem mass (MS/MS) spectra from overlapping peptides (e.g., by using multiple enzymatic digests). We have combined electron-transfer dissociation (ETD) with collision-induced dissociation (CID) and higher-energy collision-induced dissociation (HCD) fragmentation methods to boost interpretation of long, highly charged peptides and take advantage of corroborating b/y/c/z ions in CID/HCD/ETD. Using these strategies, we show that triplet CID/HCD/ETD MS/MS spectra from overlapping peptides yield de novo sequences of average length 70 AA and as long as 200 AA at up to 99% sequencing accuracy.
Methods and tools
- MS/MS Triplets: Sequencing-grade de novo analysis from overlapping CID/HCD/ETD MS/MS triplets.
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- Limitations of de novo sequencing in resolving sequence ambiguity (2025) crossref
- PepGo: a deep learning and tree search-based model for de novo peptide sequencing (2025) crossref
- Highly Robust de Novo Full-Length Protein Sequencing (2021) both
- Flying blind, or just flying under the radar? The underappreciated power of de novo methods of mass spectrometric peptide identification (2020) crossref
- A potential golden age to come—current tools, recent use cases, and future avenues for de novo sequencing in proteomics (2018) crossref
- De novo peptide sequencing by deep learning (2017) crossref
- Combining De Novo Peptide Sequencing Algorithms, A Synergistic Approach to Boost Both Identifications and Confidence in Bottom-up Proteomics (2017) crossref
- Comprehensive de Novo Peptide Sequencing from MS/MS Pairs Generated through Complementary Collision Induced Dissociation and 351 nm Ultraviolet Photodissociation (2017) both
- Evaluating de novo sequencing in proteomics: already an accurate alternative to database-driven peptide identification? (2017) crossref
- De Novo MS/MS Sequencing of Native Human Antibodies (2017) both
- Spectra library assisted de novo peptide sequencing for HCD and ETD spectra pairs (2016) both
- Revealing the functional structure of a new PLA2 K49 from Bothriopsis taeniata snake venom employing automatic “de novo” sequencing using CID/HCD/ETD MS/MS analyses (2015) crossref