Analysis of Tandem Mass Spectrometry Data with CONGA: Combining Open and Narrow Searches with Group-Wise Analysis

Searching for tandem mass spectrometry proteomics data against a database is a well-established method for assigning peptide sequences to observed spectra but typically cannot identify peptides harboring unexpected post-translational modifications (PTMs). Open modification searching aims to address...

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Bibliographic Details
Published in:Journal of proteome research 2024-06, Vol.23 (6), p.1894-1906
Main Authors: Freestone, Jack, Noble, William S., Keich, Uri
Format: Article
Language:English
Subjects:
Algorithms
Amino Acid Sequence
Databases, Protein
Humans
Peptides - analysis
Peptides - chemistry
Protein Processing, Post-Translational
Proteomics - methods
Software
Tandem Mass Spectrometry - methods
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Summary:Searching for tandem mass spectrometry proteomics data against a database is a well-established method for assigning peptide sequences to observed spectra but typically cannot identify peptides harboring unexpected post-translational modifications (PTMs). Open modification searching aims to address this problem by allowing a spectrum to match a peptide even if the spectrum’s precursor mass differs from the peptide mass. However, expanding the search space in this way can lead to a loss of statistical power to detect peptides. We therefore developed a method, called CONGA (combining open and narrow searches with group-wise analysis), that takes into account results from both types of searchesa traditional “narrow window” search and an open modification searchwhile carrying out rigorous false discovery rate control. The result is an algorithm that provides the best of both worlds: the ability to detect unexpected PTMs without a concomitant loss of power to detect unmodified peptides.
ISSN:1535-3893
1535-3907
DOI:10.1021/acs.jproteome.3c00399