MHCquant2 refines immunopeptidomics tumor antigen discovery
Confident identification of human leukocyte antigen (HLA)-presented peptides is crucial for advancing cancer immunotherapy. We present MHCquant2, a scalable and modular Nextflow pipeline integrated into nf-core as a reproducible, portable, and standardized workflow for immunopeptidomics. This integration allows a community-driven, robust solution for high-throughput analyses across operating systems and cloud infrastructures. MHCquant2 integrates open-source tools including OpenMS, DeepLC, and MS<sup>2</sup>PIP, improving peptide identifications by up to 27% across diverse MS platforms, particularly enriching low-abundant peptides. MHCquant2 demonstrates state-of-the-art performance on our novel benign<sub>MHCquant2</sub> dataset (n = 92) and expands the benign human immunopeptidome by over 160,000 unique naturally presented HLA peptides.
Authors
- Arthur Declercq (ORCID: https://orcid.org/0000-0002-9376-1399)
- Sven Nahnsen (ORCID: https://orcid.org/0000-0002-4375-0691)
- Lennart Martens (ORCID: https://orcid.org/0000-0003-4277-658X)
- Marcel Wacker (ORCID: https://orcid.org/0000-0002-8185-140X)
- Marissa L. Dubbelaar (ORCID: https://orcid.org/0000-0002-4930-1467)
- Ralf Gabriels (ORCID: https://orcid.org/0000-0002-1679-1711)
- Timo T. Sachsenberg (ORCID: https://orcid.org/0000-0002-2833-6070)
- Leon Bichmann (ORCID: https://orcid.org/0000-0001-7135-0073)
- Steffen Lemke (ORCID: https://orcid.org/0009-0009-8121-082X)
- Naomi Hoenisch Gravel (ORCID: https://orcid.org/0000-0001-9465-0175)
- Jonas Scheid (ORCID: https://orcid.org/0000-0002-5923-1343)
- Anna Dengler
- Jens Bauer (ORCID: https://orcid.org/0000-0003-3731-2385)
- Juliane S. Walz (ORCID: https://orcid.org/0000-0001-6404-7391)
Institutions
- Centre National de la Recherche Scientifique (FR)
- German Cancer Research Center (DE)
- Ghent University (BE)
- Yale University (US)
- University Children's Hospital Tübingen (DE)
- VIB-UGent Center for Medical Biotechnology (BE)
- Université de Strasbourg (FR)
- University of Tübingen (DE)
Publication Details
- Journal
- Genome biology
- Published
- 2025-09-22
- DOI
- https://doi.org/10.1186/s13059-025-03763-8
- Citations
- 2
- Primary Topic
- vaccines and immunoinformatics approaches
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Eberhard Karls Universität Tübingen
- Forschungszentrum Jülich
- German Network for Bioinformatics Infrastructure