A comprehensive proteogenomic pipeline for neoantigen discovery to advance personalized cancer immunotherapy.

Journal

Nature biotechnology

ISSN: 1546-1696

Titre abrégé: Nat Biotechnol

Pays: United States

ID NLM: 9604648

Informations de publication

Date de publication:
11 Oct 2024

Historique:

received: 04 12 2023

accepted: 04 09 2024

medline: 12 10 2024

pubmed: 12 10 2024

entrez: 11 10 2024

Statut: aheadofprint

Résumé

The accurate identification and prioritization of antigenic peptides is crucial for the development of personalized cancer immunotherapies. Publicly available pipelines to predict clinical neoantigens do not allow direct integration of mass spectrometry immunopeptidomics data, which can uncover antigenic peptides derived from various canonical and noncanonical sources. To address this, we present an end-to-end clinical proteogenomic pipeline, called NeoDisc, that combines state-of-the-art publicly available and in-house software for immunopeptidomics, genomics and transcriptomics with in silico tools for the identification, prediction and prioritization of tumor-specific and immunogenic antigens from multiple sources, including neoantigens, viral antigens, high-confidence tumor-specific antigens and tumor-specific noncanonical antigens. We demonstrate the superiority of NeoDisc in accurately prioritizing immunogenic neoantigens over recent prioritization pipelines. We showcase the various features offered by NeoDisc that enable both rule-based and machine-learning approaches for personalized antigen discovery and neoantigen cancer vaccine design. Additionally, we demonstrate how NeoDisc's multiomics integration identifies defects in the cellular antigen presentation machinery, which influence the heterogeneous tumor antigenic landscape.

Identifiants

DOI: 10.1038/s41587-024-02420-y PMID: 39394480

pubmed: 39394480

doi: 10.1038/s41587-024-02420-y

pii: 10.1038/s41587-024-02420-y

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

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