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 integr...

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Bibliographic Details
Published in:Genome Biology Vol. 26; no. 1; pp. 290 - 17
Main Authors: Scheid, Jonas, Lemke, Steffen, Hoenisch-Gravel, Naomi, Dengler, Anna, Sachsenberg, Timo, Declerq, Arthur, Gabriels, Ralf, Bauer, Jens, Wacker, Marcel, Bichmann, Leon, Martens, Lennart, Dubbelaar, Marissa L., Nahnsen, Sven, Walz, Juliane S.
Format: Journal Article
Language:English
Published: London BioMed Central 22.09.2025
Springer Nature B.V
BMC
Subjects:
Animal Genetics and Genomics
Antigens
Antigens, Neoplasm - immunology
Bioinformatics
Biomedical and Life Sciences
Cancer
Cancer immunotherapy
Data processing
Datasets
Evolutionary Biology
High performance computing
Histocompatibility antigen HLA
HLA
HLA Antigens - immunology
Human Genetics
Humans
Identification
Immunopeptidomics
Immunotherapy
Life Sciences
Mass spectrometry
Microbial Genetics and Genomics
Neoplasms - immunology
Nextflow
Nf-core
Peptides
Peptides - immunology
Pipeline
Plant Genetics and Genomics
Proteomics - methods
Search engines
Software
Open-source
Immunopeptidomics
Immunotherapy
Nextflow
Nf-core
HLA
Mass spectrometry
Pipeline
ISSN:1474-760X, 1474-7596, 1474-760X
Online Access:Get full text
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Description
Summary: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 2 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 MHCquant2 dataset ( n  = 92) and expands the benign human immunopeptidome by over 160,000 unique naturally presented HLA peptides.
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ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-025-03763-8