Comet Fragment-Ion Indexing for Enhanced Peptide Sequencing
Fragment ion indexing has significantly improved the efficiency of proteomics database search tools. This work implements fragment ion indexing in Comet, a widely used, open-source search engine. We demonstrate that this enhancement maintains scoring and identification accuracy while substantially increasing peptide spectral matching speeds across multiple applications, including open modification searches, immunopeptidomics, and real-time searches. Comet-FI reduced search speeds by up to 94%, enabling the rapid analysis of complex data types like immunopeptidomes. Fragment-ion indexing enables Comet to keep pace with modern instrumentation and expanding applications in proteomics, reinforcing its utility in diverse proteomics workflows and its integration with a wide range of proteomics tools and platforms.
Authors
- Jimmy K. Eng (ORCID: https://orcid.org/0000-0001-6352-6737)
- Christopher D. McGann (ORCID: https://orcid.org/0000-0001-9379-1910)
- Qing Yu (ORCID: https://orcid.org/0000-0003-0468-5353)
- Devin K. Schweppe (ORCID: https://orcid.org/0000-0002-3241-6276)
- Erik J. Bergstrom (ORCID: https://orcid.org/0000-0002-9939-7831)
- Lilian R. Heil (ORCID: https://orcid.org/0000-0002-9462-7327)
- Vagisha Sharma (ORCID: https://orcid.org/0000-0003-1922-439X)
Institutions
- University of Washington (US)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Brotman Baty Institute (US)
- Thermo Fisher Scientific (Israel) (IL)
Publication Details
- Journal
- Journal of Proteome Research
- Published
- 2025-06-17
- DOI
- https://doi.org/10.1021/acs.jproteome.4c01094
- Primary Topic
- Mass Spectrometry Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Pew Charitable Trusts
- W. M. Keck Foundation
- Andy Hill CARE Fund
- National Cancer Institute
- National Institute of General Medical Sciences