Anthem: a user customised tool for fast and accurate prediction of binding between peptides and HLA class I molecules

Author:

Mei Shutao1ORCID,Li Fuyi2ORCID,Xiang Dongxu1,Ayala Rochelle1,Faridi Pouya1,Webb Geoffrey I3,Illing Patricia T1,Rossjohn Jamie1,Akutsu Tatsuya4,Croft Nathan P1,Purcell Anthony W5,Song Jiangning6ORCID

Affiliation:

1. Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Australia

2. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Australia

3. Information Technology at Monash University, Australia

4. Bioinformatics Center, Institute for Chemical Research, Kyoto University, Japan

5. Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Australia

6. Monash Biomedicine Discovery Institute and Biochemistry and Molecular Biology, Monash University, Australia

Abstract

Abstract Neopeptide-based immunotherapy has been recognised as a promising approach for the treatment of cancers. For neopeptides to be recognised by CD8+ T cells and induce an immune response, their binding to human leukocyte antigen class I (HLA-I) molecules is a necessary first step. Most epitope prediction tools thus rely on the prediction of such binding. With the use of mass spectrometry, the scale of naturally presented HLA ligands that could be used to develop such predictors has been expanded. However, there are rarely efforts that focus on the integration of these experimental data with computational algorithms to efficiently develop up-to-date predictors. Here, we present Anthem for accurate HLA-I binding prediction. In particular, we have developed a user-friendly framework to support the development of customisable HLA-I binding prediction models to meet challenges associated with the rapidly increasing availability of large amounts of immunopeptidomic data. Our extensive evaluation, using both independent and experimental datasets shows that Anthem achieves an overall similar or higher area under curve value compared with other contemporary tools. It is anticipated that Anthem will provide a unique opportunity for the non-expert user to analyse and interpret their own in-house or publicly deposited datasets.

Funder

National Health and Medical Research Council of Australia

Juvenile Diabetes Research Foundation Australia

Collaborative Research Program of Institute for Chemical Research

NHMRC Principal Research Fellowship

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

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