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Codon arrangement modulates MHC-I peptides presentation

Tariq Daouda, Maude Dumont-Lagacé, Albert Feghaly, Yahya Benslimane, Rébecca Panes, Mathieu Courcelles, Mohamed Benhammadi, Lea Harrington, Pierre Thibault, François Major, Yoshua Bengio, Étienne Gagnon, Sébastien Lemieux, Claude Perreault
doi: https://doi.org/10.1101/2020.06.03.078824
Tariq Daouda
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
2Department of Biochemistry; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Maude Dumont-Lagacé
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
3Department of Medicine; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Albert Feghaly
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Yahya Benslimane
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
3Department of Medicine; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Rébecca Panes
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
4Department of Microbiology, Infectiology and Immunology; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Mathieu Courcelles
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
5Department of Chemistry; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Mohamed Benhammadi
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
3Department of Medicine; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Lea Harrington
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
3Department of Medicine; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Pierre Thibault
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
5Department of Chemistry; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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François Major
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
6Department of Informatics and Operational Research; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Yoshua Bengio
6Department of Informatics and Operational Research; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Étienne Gagnon
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
4Department of Microbiology, Infectiology and Immunology; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Sébastien Lemieux
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
2Department of Biochemistry; Université de Montréal; Montréal, Québec H3C 3J7, Canada
6Department of Informatics and Operational Research; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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Claude Perreault
1Institute for Research in Immunology and Cancer; Université de Montréal; Montréal, Québec H3C 3J7, Canada
3Department of Medicine; Université de Montréal; Montréal, Québec H3C 3J7, Canada
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  • For correspondence: claude.perreault@umontreal.ca
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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 regions, while excluding the MAP-coding codons per se. CAMAP predictions were significantly more accurate when using codon sequences than amino acid sequences. 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 binding affinity, transcript expression level and CAMAP scores was particularly useful to ameliorate predictions of MAP derived from lowly expressed transcripts. Using an in vitro assay, we showed that varying the synonymous codons in the regions flanking MAP sequences (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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Tariq Daouda is now affiliated to: (1) Broad Institute of MIT and Harvard, Cambridge, United States; (2) Center for Cancer Research, Massachusetts General Hospital, Charlestown, United States; (3) Department of Medicine, Harvard Medical School, Boston, United States; and (4) Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, United States.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Codon arrangement modulates MHC-I peptides presentation
Tariq Daouda, Maude Dumont-Lagacé, Albert Feghaly, Yahya Benslimane, Rébecca Panes, Mathieu Courcelles, Mohamed Benhammadi, Lea Harrington, Pierre Thibault, François Major, Yoshua Bengio, Étienne Gagnon, Sébastien Lemieux, Claude Perreault
bioRxiv 2020.06.03.078824; doi: https://doi.org/10.1101/2020.06.03.078824
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Codon arrangement modulates MHC-I peptides presentation
Tariq Daouda, Maude Dumont-Lagacé, Albert Feghaly, Yahya Benslimane, Rébecca Panes, Mathieu Courcelles, Mohamed Benhammadi, Lea Harrington, Pierre Thibault, François Major, Yoshua Bengio, Étienne Gagnon, Sébastien Lemieux, Claude Perreault
bioRxiv 2020.06.03.078824; doi: https://doi.org/10.1101/2020.06.03.078824

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