Abstract
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.
Competing Interest Statement
D.K.S. is a consultant and/or collaborator with ThermoFisher Scientific, AI Proteins, Genentech, and Matchpoint Therapeutics. L.R.H. is an employee of ThermoFisher Scientific. The other authors declare no competing interests.