TIMS<sup>2</sup>Rescore: A Data Dependent Acquisition-Parallel Accumulation and Serial Fragmentation-Optimized Data-Driven Rescoring Pipeline Based on MS<sup>2</sup>Rescore
The high throughput analysis of proteins with mass spectrometry (MS) is highly valuable for understanding human biology, discovering disease biomarkers, identifying therapeutic targets, and exploring pathogen interactions. To achieve these goals, specialized proteomics subfields, including plasma proteomics, immunopeptidomics, and metaproteomics, must tackle specific analytical challenges, such as an increased identification ambiguity compared to routine proteomics experiments. Technical advancements in MS instrumentation can mitigate these issues by acquiring more discerning information at higher sensitivity levels. This is exemplified by the incorporation of ion mobility and parallel accumulation and serial fragmentation (PASEF) technologies in timsTOF instruments. In addition, AI-based bioinformatics solutions can help overcome ambiguity issues by integrating more data into the identification workflow. Here, we introduce TIMS<sup>2</sup>Rescore, a data-driven rescoring workflow optimized for DDA-PASEF data from timsTOF instruments. This platform includes new timsTOF MS<sup>2</sup>PIP spectrum prediction models and IM2Deep, a new deep learning-based peptide ion mobility predictor. Furthermore, to fully streamline data throughput, TIMS<sup>2</sup>Rescore directly accepts Bruker raw mass spectrometry data and search results from ProteoScape and many other search engines, including Sage and PEAKS. We showcase TIMS<sup>2</sup>Rescore performance on plasma proteomics, immunopeptidomics (HLA class I and II), and metaproteomics data sets. TIMS<sup>2</sup>Rescore is open-source and freely available at https://github.com/compomics/tims2rescore.
Authors
- Arthur Declercq (ORCID: https://orcid.org/0000-0002-9376-1399)
- Tharan Srikumar (ORCID: https://orcid.org/0000-0003-3359-0281)
- Claudia Martelli (ORCID: https://orcid.org/0000-0002-5971-8098)
- Annica Preikschat (ORCID: https://orcid.org/0000-0002-1172-6195)
- George Rosenberger (ORCID: https://orcid.org/0000-0002-1655-6789)
- Lennart Martens (ORCID: https://orcid.org/0000-0003-4277-658X)
- Aurélie Hirschler (ORCID: https://orcid.org/0000-0001-5066-6263)
- Ralf Gabriels (ORCID: https://orcid.org/0000-0002-1679-1711)
- Stefan Tenzer (ORCID: https://orcid.org/0000-0003-3034-0017)
- Dennis Trede
- David Gómez-Zepeda (ORCID: https://orcid.org/0000-0002-9467-1213)
- Sven Degroeve (ORCID: https://orcid.org/0000-0001-8349-3370)
- Jonas Scheid (ORCID: https://orcid.org/0000-0002-5923-1343)
- Jonathan R. Krieger (ORCID: https://orcid.org/0000-0001-6491-2672)
- Tim Van Den Bossche (ORCID: https://orcid.org/0000-0002-5916-2587)
- Christine Carapito (ORCID: https://orcid.org/0000-0002-0079-319X)
- Juliane S. Walz (ORCID: https://orcid.org/0000-0001-6404-7391)
- Robbin Bouwmeester (ORCID: https://orcid.org/0000-0001-6807-7029)
- Jeewan Babu Rijal (ORCID: https://orcid.org/0009-0009-6839-9947)
- Robbe Devreese (ORCID: https://orcid.org/0000-0002-3432-1502)
- Caroline Jachmann (ORCID: https://orcid.org/0009-0000-4679-7295)
Institutions
- Centre National de la Recherche Scientifique (FR)
- German Cancer Research Center (DE)
- Bruker (United States) (US)
- Johannes Gutenberg University Mainz (DE)
- Heidelberg University (DE)
- Ghent University Hospital (BE)
- Ghent University (BE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Helmholtz Institute Mainz (DE)
- Bruker (United Kingdom) (GB)
- Institute of Immunology (HR)
- Bruker (Germany) (DE)
- Bruker (Switzerland) (CH)
- VIB-UGent Center for Medical Biotechnology (BE)
- Bruker (Canada) (CA)
- Quantitative Biology Center
- Université de Strasbourg (FR)
- University of Tübingen (DE)
Publication Details
- Journal
- Journal of Proteome Research
- Published
- 2025-02-07
- DOI
- https://doi.org/10.1021/acs.jproteome.4c00609
- Citations
- 17
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 12.10
Funders
- Deutsches Krebsforschungszentrum
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Bundesministerium für Bildung und Forschung
- Fonds Wetenschappelijk Onderzoek
- Université de Strasbourg
- Universiteit Gent
- Centre National de la Recherche Scientifique
- Deutsche Krebshilfe
- Vlaamse regering
- Deutschen Konsortium für Translationale Krebsforschung
- Heidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-Gemeinschaft
- HORIZON EUROPE Framework Programme
- CHIST-ERA