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Cited by 11Advanced Proteomics Techniques and ApplicationsMass Spectrometry Techniques and ApplicationsProtein Structure and Dynamics

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Proteome-wide non-cleavable crosslink identification with MS Annika 3.0 reveals the structure of the C. elegans Box C/D complex

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Birklbauer, Micha J., Müller, Fränze, Geetha, Sowmya Sivakumar, Matzinger, Manuel, Mechtler, Karl, Dorfer, Viktoria·2024·Communications Chemistry
DOI 10.1038/s42004-024-01386-xPMC PMC11659399

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Abstract

The field of crosslinking mass spectrometry has seen substantial advancements over the past decades, enabling the structural analysis of proteins and protein complexes and serving as a powerful tool in protein-protein interaction studies. However, data analysis of large non-cleavable crosslink studies is still a mostly unsolved problem due to its n-squared complexity. We here introduce an algorithm for the identification of non-cleavable crosslinks implemented in our crosslinking search engine MS Annika that is based on sparse matrix multiplication and allows for proteome-wide searches on commodity hardware. We compare our algorithm to other state-of-the-art crosslinking search engines commonly used in the field and conclude that MS Annika unifies high sensitivity, accurate FDR estimation and computational performance, outperforming competing tools. Application of this algorithm enabled us to employ a proteome-wide search of C. elegans nuclei samples, where we were able to uncover previously unknown protein interactions and conclude a comprehensive structural analysis that provides a detailed view of the Box C/D complex. Moreover, our algorithm will enable researchers to conduct similar studies that were previously unfeasible.

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Metadata

Authors
Birklbauer, M. J., Müller, F., Geetha, S. S., Matzinger, M., Mechtler, K., & Dorfer, V.
Affiliations
  • Johannes Kepler University of Linz (AT)
  • Research Institute of Molecular Pathology (AT)
  • University of Vienna (AT)
  • Institute of Molecular Biotechnology (AT)
  • University of Applied Sciences Upper Austria (AT)
Corresponding author
  • Birklbauer, Micha J.
  • Dorfer, Viktoria
ORCID
Venue
Communications Chemistry
Publisher
Springer Science and Business Media LLC
Published
2024-12-19
Volume
7
Issue
1
Pages
300-300
ISSN
2399-3669 (ISSN-L)
DOI
10.1038/s42004-024-01386-x
PMC
PMC11659399
OpenAlex
W4405577267
Cited by
11
References
2
Citations by year
2026: 6 · 2025: 4 · 2024: 1
FWCI
1.37
Type
journal article
Language
en
Update notices
correction (2025-02-27)
Open access
Licence
Locations
  • Communications Chemistry (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Austrian Science Fund (P35045-B, ESP566, SFB F 8805-B)
  • Österreichische Forschungsförderungsgesellschaft (AT-SCP)
  • Vienna Science and Technology Fund (LS20-079)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
sparse matrix multiplication, protein-protein interaction, protein complex structure, false discovery rate estimation, computational performance

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