TY - JOUR
T1 - MS Annika
T2 - A New Cross-Linking Search Engine
AU - Pirklbauer, Georg J.
AU - Stieger, Christian E.
AU - Matzinger, Manuel
AU - Winkler, Stephan
AU - Mechtler, Karl
AU - Dorfer, Viktoria
N1 - Funding Information:
We would like to thank J. Griss for proofreading the manuscript. Work in the Mechtler lab was financially supported by the EPIC-XS, project number 823839, the Horizon 2020 Program of the European Union, and the ERA-CAPS I 3686 project of the Austrian Science Fund. Work at the University of Applied Sciences (FH OOe) was funded by the TiMED Center and by the Basic Research Programme of FH OOe (PPI-ID). Figures have been created using Thermo Proteome Discoverer 2.4 and 2.5, R Studio, canva.com and xiView. We thank the developers for providing such great tools.
Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/5/7
Y1 - 2021/5/7
N2 - 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.
AB - 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.
KW - bioinformatics
KW - cross-linking
KW - MS/MS
KW - PPI
KW - protein-protein-interaction
KW - search engine
KW - tandem mass spectrometry
KW - XL-MS
KW - Cross-Linking Reagents
KW - Peptides
KW - Proteome
KW - Mass Spectrometry
KW - Search Engine
UR - http://www.scopus.com/inward/record.url?scp=85105113441&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.0c01000
DO - 10.1021/acs.jproteome.0c01000
M3 - Article
C2 - 33852321
SN - 1535-3893
VL - 20
SP - 2560
EP - 2569
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 5
ER -