Journal Article

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

Dumont-Lagacé, Maude, Daouda, Tariq, Benhammadi, Mohamed, Harrington, Lea, Perreault, Claude, Major, François, Gagnon, Étienne, Feghaly, Albert, Courcelles, Mathieu, Benslimane, Yahya, Bengio, Yoshua, Lemieux, Sébastien, Panes, Rébecca, Thibault, Pierre

2021

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Algorithms / Amino Acid Sequence / Amino acids / Analysis / Artificial neural networks / Biology and Life Sciences / Biosynthesis / CD8 antigen / Cell surface / Codon / Codon - chemistry / Codon - genetics / Codon - metabolism / Codons / Computational Biology - methods / Datasets / Gene expression / Gene sequencing / Genetic aspects / Histocompatibility Antigens Class I - chemistry / Histocompatibility Antigens Class I - genetics / Histocompatibility Antigens Class I - metabolism / Humans / Identification and classification / Influence / Lymphocytes / Lymphocytes T / Major histocompatibility complex / Mass spectrometry / Medicine and Health Sciences / Messenger RNA / Methods / Neural networks / Neural Networks, Computer / Peptides / Post-translation / Predictions / Proteins / Research and Analysis Methods / Scientific imaging / Transcription / Transcriptomes / Translation / Viruses