pNovo+: De Novo Peptide Sequencing Using Complementary HCD and ETD Tandem Mass Spectra
peer-reviewed · Journal of Proteome Research · 2013
| Date | 2013-02-01 |
| Type | peer-reviewed |
| Venue | Journal of Proteome Research |
| Publisher | American Chemical Society |
| Contribution | algorithm |
| DOI | 10.1021/pr3006843 |
| Citations (OpenAlex) | 107 |
| Venue 2-year citedness | 3.48 |
Abstract
De novo peptide sequencing is the only tool for extracting peptide sequences directly from tandem mass spectrometry (MS) data without any protein database. However, neither the accuracy nor the efficiency of de novo sequencing has been satisfactory, mainly due to incomplete fragmentation information in experimental spectra. Recent advancement in MS technology has enabled acquisition of higher energy collisional dissociation (HCD) and electron transfer dissociation (ETD) spectra of the same precursor. These spectra contain complementary fragmentation information and can be collected with high resolution and high mass accuracy. Taking these advantages, we have developed a new algorithm called pNovo+, which greatly improves the accuracy and speed of de novo sequencing. On tryptic peptides, 86% of the topmost candidate sequences deduced by pNovo+ from HCD + ETD spectral pairs matched the database search results, and the success rate reached 95% if the top three candidates were included, which was much higher than using only HCD (87%) or only ETD spectra (57%). On Asp-N, Glu-C, or Elastase digested peptides, 69-87% of the HCD + ETD spectral pairs were correctly identified by pNovo+ among the topmost candidates, or 84-95% among the top three. On average, it takes pNovo+ only 0.018 s to extract the sequence from a spectrum or spectral pair on a common personal computer. This is more than three times as fast as other de novo sequencing programs. The increase of speed is mainly due to pDAG, a component algorithm of pNovo+. pDAG finds the k longest paths in a directed acyclic graph without the antisymmetry restriction. We have verified that the antisymmetry restriction is unnecessary for high resolution, high mass accuracy data. The extensive use of HCD and ETD spectral information and the pDAG algorithm make pNovo+ an excellent de novo sequencing tool.
Methods and tools
- pNovo+: Complementary HCD + ETD spectra
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- Algorithms for de-novo sequencing of peptides by tandem mass spectrometry: A review (2023) crossref
- Denovo-GCN: De Novo Peptide Sequencing by Graph Convolutional Neural Networks (2023) both
- Multienzyme deep learning models improve peptide de novo sequencing by mass spectrometry proteomics (2023) both
- 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
- Deep Learning in Proteomics (2020) both
- pNovo 3: precise de novo peptide sequencing using a learning-to-rank framework (2019) both
- Postnovo: Postprocessing Enables Accurate and FDR-Controlled de Novo Peptide Sequencing (2018) crossref
- A potential golden age to come—current tools, recent use cases, and future avenues for de novo sequencing in proteomics (2018) crossref
- pSite: Amino Acid Confidence Evaluation for Quality Control of De Novo Peptide Sequencing and Modification Site Localization (2017) 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) crossref
- Evaluating de novo sequencing in proteomics: already an accurate alternative to database-driven peptide identification? (2017) crossref
- Open-pNovo: De Novo Peptide Sequencing with Thousands of Protein Modifications (2017) crossref
- De novo peptide sequencing using CID and HCD spectra pairs (2016) crossref
- Peptide de novo sequencing of mixture tandem mass spectra (2016) both
- UVnovo: A de Novo Sequencing Algorithm Using Single Series of Fragment Ions via Chromophore Tagging and 351 nm Ultraviolet Photodissociation Mass Spectrometry (2016) both
- Application of de Novo Sequencing to Large-Scale Complex Proteomics Data Sets (2016) crossref
- Lessons in de novo peptide sequencing by tandem mass spectrometry (2015) both
- High-Confidence de Novo Peptide Sequencing Using Positive Charge Derivatization and Tandem MS Spectra Merging (2013) crossref