Journal
JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 5, Pages 2560-2569Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.0c01000
Keywords
tandem mass spectrometry; cross-linking; bioinformatics; search engine; MS/MS; XL-MS; protein-protein-interaction; PPI
Categories
Funding
- EPIC-XS, project [823839]
- Horizon 2020 Program of the European Union
- Austrian Science Fund [ERACAPS I 3686]
- TiMED Center
- Basic Research Programme of FH OOe (PPI-ID)
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Cross-linking mass spectrometry (XL-MS) has enabled insights into protein structures and interactions, with cleavable cross-linkers further reducing search space and promoting proteome-wide studies. However, some search engines struggle with validating identified cross-linked peptides and estimating false discovery rates (FDR). The new search engine MS Annika provides realistic FDR estimates without the need for arbitrary score cutoffs, offering on average 44% more identifications at a similar or better true FDR compared to other tools.
Cross-linking mass spectrometry (XL-MS) has become a powerful technique that enables insights into protein structures and protein interactions. The development of cleavable cross-linkers has further promoted XL-MS through search space reduction, thereby allowing for proteome-wide studies. These new analysis possibilities foster the development of new cross-linkers, which not every search engine can deal with out of the box. In addition, some search engines for XL-MS data also struggle with the validation of identified cross-linked peptides, that is, false discovery rate (FDR) estimation, as FDR calculation is hampered by the fact that not only one but two peptides in a single spectrum have to be correct. We here present our new search engine, MS Annika, which can identify cross-linked peptides in MS2 spectra from a wide variety of cleavable cross-linkers. We show that MS Annika provides realistic estimates of FDRs without the need of arbitrary score cutoffs, being able to provide on average 44% more identifications at a similar or better true FDR than comparable tools. In addition, MS Annika can be used on proteome-wide studies due to fast, parallelized processing and provides a way to visualize the identified cross-links in protein 3D structures.
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