SILVI, an open-source pipeline for T-cell epitope selection

PLoS One. 2022 Sep 7;17(9):e0273494. doi: 10.1371/journal.pone.0273494. eCollection 2022.

Abstract

High-throughput screening of available genomic data and identification of potential antigenic candidates have promoted the development of epitope-based vaccines and therapeutics. Several immunoinformatic tools are available to predict potential epitopes and other immunogenicity-related features, yet it is still challenging and time-consuming to compare and integrate results from different algorithms. We developed the R script SILVI (short for: from in silico to in vivo), to assist in the selection of the potentially most immunogenic T-cell epitopes from Human Leukocyte Antigen (HLA)-binding prediction data. SILVI merges and compares data from available HLA-binding prediction servers, and integrates additional relevant information of predicted epitopes, namely BLASTp alignments with host proteins and physical-chemical properties. The two default criteria applied by SILVI and additional filtering allow the fast selection of the most conserved, promiscuous, strong binding T-cell epitopes. Users may adapt the script at their discretion as it is written in open-source R language. To demonstrate the workflow and present selection options, SILVI was used to integrate HLA-binding prediction results of three example proteins, from viral, bacterial and parasitic microorganisms, containing validated epitopes included in the Immune Epitope Database (IEDB), plus the Human Papillomavirus (HPV) proteome. Applying different filters on predicted IC50, hydrophobicity and mismatches with host proteins allows to significantly reduce the epitope lists with favourable sensitivity and specificity to select immunogenic epitopes. We contemplate SILVI will assist T-cell epitope selections and can be continuously refined in a community-driven manner, helping the improvement and design of peptide-based vaccines or immunotherapies. SILVI development version is available at: github.com/JoanaPissarra/SILVI2020 and https://doi.org/10.5281/zenodo.6865909.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Epitopes, T-Lymphocyte* / genetics
  • Humans
  • Lymphocyte Activation
  • Proteins
  • Vaccines*

Substances

  • Epitopes, T-Lymphocyte
  • Proteins
  • Vaccines

Grants and funding

This research received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement N° 642609, from the French National Research Institute for Sustainable Development (Institut de Recherche pour le Developpement), and from the French Government (Agence Nationale de la Recherche) Investissement d’Avenir programme, Laboratoire d’Excellence (LabEx) “French Parasitology Alliance For Health Care” (ANR-11-LABX-0024-PARAFRAP). JP was partly supported by Fondation des Treilles Young Researcher prize (« La Fondation des Treilles, créée par Anne Gruner Schlumberger, a notamment pour vocation d’ouvrir et de nourrir le dialogue entre les sciences et les arts afin de faire progresser la création et la recherche contemporaines. Elle accueille également des chercheurs et des écrivains dans le domaine des Treilles (Var) www.les-treilles.com »). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.