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Peer-reviewedCC BY 4.0GigaScience

Epitope Generation Gateway: A biological context-dependent approach to cancer vaccine development

  • Luca Mannino1
  • Michele Fratello1
  • Jacopo Chiaro2,3,4,5
  • Federica D’Alessio2,3,4,5
  • Emanuele Di Lieto1
  • Minna Niittykoski6
  • Angela Serra1,7,8
  • Seppo Ylä-Herttuala6,9
  • Vincenzo Cerullo2,3,4,5,10
  • Antonio Federico1,7,8
  • Dario Greco1,8
10 affiliations
  1. 1Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, Kauppi, 33520 , Tampere ,
  2. 2Department of Pharmaceutical Biosciences, Faculty of Pharmacy ImmunoViroTherapy Lab, Drug Research Program, University of Helsinki, Viikinkaari 5 E, Viikki, 00790 , Helsinki ,
  3. 3Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Viikinkaari 5 D, Viikki, 00790 , Helsinki ,
  4. 4Translational Immunology Program (TRIMM), Faculty of Medicine Helsinki University, University of Helsinki, Haartmaninkatu 8, Meilahti, 00290 , Helsinki ,
  5. 5Digital Precision Cancer Medicine Flagship (iCAN), University of Helsinki. Haartmaninkatu 8, Meilahti, 00290 , Helsinki ,
  6. 6A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70211 , Kuopio ,
  7. 7Tampere Institute for Advanced Study, Tampere University, Kalevantie 4, City Centre Campus, 33100 , Tampere ,
  8. 8Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, Viikki, 00790 , Helsinki ,
  9. 9Heart Center and Gene Therapy Unit, Kuopio University Hospital, Puijonlaaksontie 2, 70210 Kuopio , Kuopio ,
  10. 10Department of Molecular Medicine and Medical Biotechnology and CEINGE, Naples University Federico II, Via Sergio Pansini 5, Zona Ospedaliera, 80131 , Naples ,
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Abstract

Background: Personalized neoantigen discovery requires tools that not only identify putative epitopes but also prioritize candidates using biological features relevant to tumor fitness and immune escape. Here, we present Epitope Generation Gateway (EGG), a containerized pipeline that streamlines discovery and prioritization across variant types and human leukocyte antigen (HLA) contexts. EGG coordinates established components, Mutect2 for somatic single nucleotide variations (SNVs) and indels, STAR-Fusion for fusion events, ArcasHLA for HLA typing, and pVACtools for epitope sequence prediction, then augments peptide-level scores with biological context. For each patient, EGG builds co-expression and protein–protein interaction networks, uses centrality measures and CRISPR dependency data (DepMap) to flag genes important for tumor fitness, and annotates source genes with gene ontology terms, Hallmarks of Cancer processes, and IntOGen driver status. Results: This multi-layer information supports ranking of candidates that are predicted to be presented and that arise from genes essential to tumor fitness or embedded in key pathways, providing a framework to nominate epitopes whose source genes may be less dispensable under immune pressure. As a case study, we applied EGG to 30 TCGA skin cutaneous melanoma patients, demonstrating end-to-end execution and producing prioritized epitopes that emphasize peptides and alterations in high-centrality, dependency-supported essential genes. Conclusions: Overall, EGG links epitope prioritization to tumor systems biology and evolutionary rationale, prioritizing biologically contextualized cancer vaccine candidates from SNVs, indels, fusions, and splicing-derived epitopes while streamlining dataset analysis. EGG is available from GitHub at https://github.com/fhaive/epitope_generation_gateway.

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Cite

BibTeXRIS
BibTeX
@article{mannino2026epitope,
  title = {{Epitope Generation Gateway: A biological context-dependent approach to cancer vaccine development}},
  author = {Luca Mannino and Michele Fratello and Jacopo Chiaro and Federica D’Alessio and Emanuele Di Lieto and Minna Niittykoski and Angela Serra and Seppo Ylä-Herttuala and Vincenzo Cerullo and Antonio Federico and Dario Greco},
  journal = {GigaScience},
  year = {2026},
  month = oct,
  doi = {10.1093/gigascience/giag095},
  url = {https://academic.oup.com/gigascience/article/doi/10.1093/gigascience/giag095/8859085},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Epitope Generation Gateway: A biological context-dependent approach to cancer vaccine development
AU  - Luca Mannino
AU  - Michele Fratello
AU  - Jacopo Chiaro
AU  - Federica D’Alessio
AU  - Emanuele Di Lieto
AU  - Minna Niittykoski
AU  - Angela Serra
AU  - Seppo Ylä-Herttuala
AU  - Vincenzo Cerullo
AU  - Antonio Federico
AU  - Dario Greco
PY  - 2026
DA  - 2026/10/01
JO  - GigaScience
DO  - 10.1093/gigascience/giag095
UR  - https://academic.oup.com/gigascience/article/doi/10.1093/gigascience/giag095/8859085
AB  - Background: Personalized neoantigen discovery requires tools that not only identify putative epitopes but also prioritize candidates using biological features relevant to tumor fitness and immune escape. Here, we present Epitope Generation Gateway (EGG), a containerized pipeline that streamlines discovery and prioritization across variant types and human leukocyte antigen (HLA) contexts. EGG coordinates established components, Mutect2 for somatic single nucleotide variations (SNVs) and indels, STAR-Fusion for fusion events, ArcasHLA for HLA typing, and pVACtools for epitope sequence prediction, then augments peptide-level scores with biological context. For each patient, EGG builds co-expression and protein–protein interaction networks, uses centrality measures and CRISPR dependency data (DepMap) to flag genes important for tumor fitness, and annotates source genes with gene ontology terms, Hallmarks of Cancer processes, and IntOGen driver status. Results: This multi-layer information supports ranking of candidates that are predicted to be presented and that arise from genes essential to tumor fitness or embedded in key pathways, providing a framework to nominate epitopes whose source genes may be less dispensable under immune pressure. As a case study, we applied EGG to 30 TCGA skin cutaneous melanoma patients, demonstrating end-to-end execution and producing prioritized epitopes that emphasize peptides and alterations in high-centrality, dependency-supported essential genes. Conclusions: Overall, EGG links epitope prioritization to tumor systems biology and evolutionary rationale, prioritizing biologically contextualized cancer vaccine candidates from SNVs, indels, fusions, and splicing-derived epitopes while streamlining dataset analysis. EGG is available from GitHub at https://github.com/fhaive/epitope_generation_gateway.
SN  - 2047-217X
ER  -