CAMAP - Artificial neural networks unveil the role of codon arrangement in modulating MHC-I peptides presentation

Abstract

MHC-I associated peptides (MAPs) play a central role in the elimination of virus-infected and neoplastic cells by CD8 T cells. However, accurately predicting the MAP repertoire remains difficult, because only a fraction of the transcriptome generates MAPs. In this study, we investigated whether codon arrangement (usage and placement) regulates MAP biogenesis. We developed an artificial neural network called Codon Arrangement MAP Predictor (CAMAP), predicting MAP presentation solely from mRNA sequences flanking the MAP-coding codons (MCCs), while excluding the MCC per se. CAMAP predictions were significantly more accurate when using original codon sequences than shuffled codon sequences which reflect amino acid usage. Furthermore, predictions were independent of mRNA expression and MAP binding affinity to MHC-I molecules and applied to several cell types and species. Combining MAP ligand scores, transcript expression level and CAMAP scores was particularly useful to increase MAP prediction accuracy. Using an in vitro assay, we showed that varying the synonymous codons in the regions flanking the MCCs (without changing the amino acid sequence) resulted in significant modulation of MAP presentation at the cell surface. Taken together, our results demonstrate the role of codon arrangement in the regulation of MAP presentation and support integration of both translational and post-translational events in predictive algorithms to ameliorate modeling of the immunopeptidome.,

Publication
PLOS Computational Biology
Tariq Daouda
Tariq Daouda
Étudiant au doctorat en bio-informatique (2011-2018 avec Claude Perrault, IRIC)
Mathieu Courcelles
Mathieu Courcelles
Étudiant au doctorat en bio-informatique (2008-2012 avec Pierre Thibault, IRIC)
Sébastien Lemieux
Sébastien Lemieux
Principal Investigator

Principal Investigator, Functional and Structural Bioinformatics Research Unit, IRIC | Scientific direction of the Bioinformatics platform | Associate Professor, Department of Biochemistry and Molecular Medicine, Université de Montréal