MSFragger-DDA+ enhances peptide identification sensitivity with full isolation window search

Fengchao Yu (), Yamei Deng and Alexey I. Nesvizhskii ()
Additional contact information
Fengchao Yu: University of Michigan
Yamei Deng: University of Michigan
Alexey I. Nesvizhskii: University of Michigan

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Liquid chromatography-mass spectrometry based proteomics, particularly in the bottom-up approach, relies on the digestion of proteins into peptides for subsequent separation and analysis. The most prevalent method for identifying peptides from data-dependent acquisition mass spectrometry data is database search. Traditional tools typically focus on identifying a single peptide per tandem mass spectrum, often neglecting the frequent occurrence of peptide co-fragmentations leading to chimeric spectra. Here, we introduce MSFragger-DDA+, a database search algorithm that enhances peptide identification by detecting co-fragmented peptides with high sensitivity and speed. Utilizing MSFragger’s fragment ion indexing algorithm, MSFragger-DDA+ performs a comprehensive search within the full isolation window for each tandem mass spectrum, followed by robust feature detection, filtering, and rescoring procedures to refine search results. Evaluation against established tools across diverse datasets demonstrated that, integrated within the FragPipe computational platform, MSFragger-DDA+ significantly increases identification sensitivity while maintaining stringent false discovery rate control. It is also uniquely suited for wide-window acquisition data. MSFragger-DDA+ provides an efficient and accurate solution for peptide identification, enhancing the detection of low-abundance co-fragmented peptides. Coupled with the FragPipe platform, MSFragger-DDA+ enables more comprehensive and accurate analysis of proteomics data.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58728-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58728-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58728-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().