Flying blind, or just flying under the radar? The underappreciated power of de novo methods of mass spectrometric peptide identification
peer-reviewed · Protein Science · 2020
| Date | 2020-09-01 |
| Type | peer-reviewed |
| Venue | Protein Science |
| Publisher | Wiley |
| Contribution | review |
| DOI | 10.1002/pro.3919 |
| Citations (OpenAlex) | 40 |
| Venue 2-year citedness | 3.27 |
Abstract
Mass spectrometry-based proteomics is a popular and powerful method for precise and highly multiplexed protein identification. The most common method of analyzing untargeted proteomics data is called database searching, where the database is simply a collection of protein sequences from the target organism, derived from genome sequencing. Experimental peptide tandem mass spectra are compared to simplified models of theoretical spectra calculated from the translated genomic sequences. However, in several interesting application areas, such as forensics, archaeology, venomics, and others, a genome sequence may not be available, or the correct genome sequence to use is not known. In these cases, de novo peptide identification can play an important role. De novo methods infer peptide sequence directly from the tandem mass spectrum without reference to a sequence database, usually using graph-based or machine learning algorithms. In this review, we provide a basic overview of de novo peptide identification methods and applications, briefly covering de novo algorithms and tools, and focusing in more depth on recent applications from venomics, metaproteomics, forensics, and characterization of antibody drugs.
Methods and tools
- Flying under the radar review: O’Bryon, Jenson & Merkley 2020 Protein Science review arguing that de novo peptide identification is under-appreciated relative to database-search methods, with concrete forensic / non-model / immunopeptidomic cases where it wins.
Cites (31)
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Cited by (14)
- De novo peptide databases enable protein-based stable isotope probing of microbial communities with up to species-level resolution (2025) both
- Limitations of de novo sequencing in resolving sequence ambiguity (2025) both
- Homo-Tag-Assembler Assay for Full-Length Antibody Sequencing (2025) crossref
- MARLOWE: Taxonomic Characterization of Unknown Samples for Forensics Using De Novo Peptide Identification (2025) crossref
- MARLOWE: An Untargeted Proteomics, Statistical Approach to Taxonomic Classification for Forensics (2025) crossref
- Metaproteomics Beyond Databases: Addressing the Challenges and Potentials of De Novo Sequencing (2025) crossref
- De novo peptide databases enable protein-based stable isotope probing of microbial communities with up to species-level resolution (2024) crossref
- Algorithms for de-novo sequencing of peptides by tandem mass spectrometry: A review (2023) crossref
- Comprehensive evaluation of peptide de novo sequencing tools for monoclonal antibody assembly (2023) both
- Current state, existing challenges, and promising progress for de novo sequencing and assembly of monoclonal antibodies (2022) both
- Metaproteomic Characterization of Forensic Samples (2022) crossref
- Affinity Selection from Synthetic Peptide Libraries Enabled by De Novo MS/MS Sequencing (2022) both
- Protein cycling in the eastern tropical North Pacific oxygen‐deficient zone: A de novo‐discovery peptidomic approach (2022) crossref
- Highly Robust de Novo Full-Length Protein Sequencing (2021) both