B-S.B.57: Epitope Generation Gateway (EGG): A biological context dependent approach to cancer vaccine development
Personalized cancer vaccines require neoantigen selection strategies that consider not only peptide presentation but also the biological importance of the altered gene within the tumor. We developed Epitope Generation Gateway (EGG), a modular Snakemake workflow for end-to-end neoantigen discovery and prioritization from raw DNA and RNA sequencing data. EGG identifies candidate epitopes arising from somatic single nucleotide variants, indels, gene fusions, and alternative splicing events, while also supporting HLA typing and downstream ranking. What distinguishes EGG from existing pipelines is the integration of patient-specific biological context into neoantigen prioritization. Using RNA sequencing data, EGG constructs personalized gene co-expression networks and combines network centrality with protein interaction information, gene essentiality data, expression, and peptide binding-related features. This allows prioritization of neoantigens derived from genes more likely to be functionally necessary for tumor fitness and less likely to be lost through immune escape. As a case study, we applied EGG to TCGA skin cutaneous melanoma cases and obtained prioritized neoantigen candidates. Current work extends these analyses to a cohort of Finnish melanoma patient data. In parallel, this work connects to development of the In Vitro Immune Systems Resource for Precision Medicine, a translational resource integrating neoantigen analyses from approximately 2,000 cell lines with HLA typing and immune features, including KIR, TCR, and BCR information, supporting neoantigen studies and guide selection of suitable cell combinations for downstream co-culture experiments Overall, EGG provides a reproducible framework for biologically informed cancer vaccine target discovery while supporting the identification of more durable neoantigen candidates.
Co-authors: Michele Fratello, Jacopo Chiaro, Federica D'Alessio, Ada Taubert, Lorenzo Campini, Emanuele Di Lieto, Minna Niittykoski, Angela Serra, Jack Morikka, Seppo Ylä-Herttuala, Vincenzo Cerullo, Antonio Federico, Dario Greco
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