Huber et al. developed a pipeline (Neodisc) integrating WGS/WES, RNAseq, and immunopeptidomics to predict and prioritize antigenic peptides derived from mutations, TSAs, TAAs, oncoviruses, or non-canonical transcripts for clinical use. Neodisc more efficiently ranked peptide candidates than existing approaches. LOH events impacting HLA alleles and other defects in the tumor antigen processing machinery could be analyzed to account for peptide presentation capacity, and results from multiple biopsies could be merged into one pipeline to study tumor heterogeneity.
Contributed by Morgan Janes
ABSTRACT: 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.
Author Info: (1) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lau
Author Info: (1) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (2) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (3) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. SIB Swiss Institute of Bioinformatics, Quartier Sorge, Btiment Amphiple, Lausanne, Switzerland. (4) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (5) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (6) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (7) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (8) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (9) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (10) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. SIB Swiss Institute of Bioinformatics, Quartier Sorge, Btiment Amphiple, Lausanne, Switzerland. (11) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (12) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (13) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (14) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. SIB Swiss Institute of Bioinformatics, Quartier Sorge, Btiment Amphiple, Lausanne, Switzerland. (15) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (16) Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (17) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (18) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (19) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (20) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (21) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. SIB Swiss Institute of Bioinformatics, Quartier Sorge, Btiment Amphiple, Lausanne, Switzerland. (22) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (23) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (24) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. (25) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Department of Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. (26) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. (27) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (28) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. AGORA Cancer Research Center, Lausanne, Switzerland. (29) Department of Oncology, University of Lausanne (UNIL) and Lausanne University Hospital (CHUV), Lausanne, Switzerland. michal.bassani@chuv.ch. Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland. michal.bassani@chuv.ch. AGORA Cancer Research Center, Lausanne, Switzerland. michal.bassani@chuv.ch. Center of Experimental Therapeutics, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. michal.bassani@chuv.ch.
