{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:51:50Z","timestamp":1767178310515,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009482","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000521","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["705604"],"award-info":[{"award-number":["705604"]}],"id":[{"id":"10.13039\/501100000521","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000521","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["705714"],"award-info":[{"award-number":["705714"]}],"id":[{"id":"10.13039\/501100000521","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oncopole"},{"DOI":"10.13039\/100009447","name":"Leukemia and Lymphoma Society of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Katelyn Bedard Bone Marrow Association"},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cole Foundation"},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["148936"],"award-info":[{"award-number":["148936"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["163051"],"award-info":[{"award-number":["163051"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["MOP-133726"],"award-info":[{"award-number":["MOP-133726"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    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\n                    <jats:italic>per se<\/jats:italic>\n                    . 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\n                    <jats:italic>in vitro<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009482","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T19:01:14Z","timestamp":1634929274000},"page":"e1009482","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["CAMAP: Artificial neural networks unveil the role of codon arrangement in modulating MHC-I peptides presentation"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7086-8321","authenticated-orcid":true,"given":"Tariq","family":"Daouda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-0975","authenticated-orcid":true,"given":"Maude","family":"Dumont-Lagac\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7929-415X","authenticated-orcid":true,"given":"Albert","family":"Feghaly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahya","family":"Benslimane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-0416","authenticated-orcid":true,"given":"R\u00e9becca","family":"Panes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Courcelles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-7734","authenticated-orcid":true,"given":"Mohamed","family":"Benhammadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-2744","authenticated-orcid":true,"given":"Lea","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Thibault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Major","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshua","family":"Bengio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5815-9768","authenticated-orcid":true,"given":"\u00c9tienne","family":"Gagnon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Lemieux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-7383","authenticated-orcid":true,"given":"Claude","family":"Perreault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"pcbi.1009482.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2014.10.012","article-title":"The nature of self for T cells\u2014a systems-level perspective","volume":"34","author":"DP Granados","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"pcbi.1009482.ref002","doi-asserted-by":"crossref","first-page":"e07661","DOI":"10.7554\/eLife.07661","article-title":"An open-source computational and data resource to analyze digital maps of immunopeptidomes","volume":"4","author":"E Caron","year":"2015","journal-title":"eLife"},{"key":"pcbi.1009482.ref003","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1146\/annurev.immunol.24.021605.090600","article-title":"T Cells as a Self-Referential, Sensory Organ","volume":"25","author":"MM Davis","year":"2007","journal-title":"Annu Rev Immunol"},{"key":"pcbi.1009482.ref004","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.aaa4971","article-title":"Neoantigens in cancer immunotherapy","volume":"348","author":"TN Schumacher","year":"2015","journal-title":"Science"},{"key":"pcbi.1009482.ref005","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/msb.2011.68","article-title":"The MHC I immunopeptidome conveys to the cell surface an integrative view of cellular regulation","volume":"7","author":"E Caron","year":"2011","journal-title":"Mol Syst Biol"},{"key":"pcbi.1009482.ref006","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nri3084","article-title":"Towards a systems understanding of MHC class I and MHC class II antigen presentation","volume":"11","author":"J Neefjes","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"pcbi.1009482.ref007","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.4049\/jimmunol.1600808","article-title":"Unsupervised HLA Peptidome Deconvolution Improves Ligand Prediction Accuracy and Predicts Cooperative Effects in Peptide\u2013HLA Interactions","volume":"197","author":"M Bassani-Sternberg","year":"2016","journal-title":"J Immunol"},{"key":"pcbi.1009482.ref008","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13073-016-0288-x","article-title":"NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets","volume":"8","author":"M Nielsen","year":"2016","journal-title":"Genome Med"},{"key":"pcbi.1009482.ref009","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00018-005-4528-2","article-title":"Modeling the MHC class I pathway by combining predictions of proteasomal cleavage,TAP transport and MHC class I binding","volume":"62","author":"S Tenzer","year":"2005","journal-title":"Cell Mol Life Sci CMLS"},{"key":"pcbi.1009482.ref010","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s00251-005-0781-7","article-title":"The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage","volume":"57","author":"M Nielsen","year":"2005","journal-title":"Immunogenetics"},{"key":"pcbi.1009482.ref011","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.immuni.2017.02.007","article-title":"Mass Spectrometry Profiling of HLA-Associated Peptidomes in Mono-allelic Cells Enables More Accurate Epitope Prediction","volume":"46","author":"JG Abelin","year":"2017","journal-title":"Immunity"},{"key":"pcbi.1009482.ref012","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.coi.2017.04.007","article-title":"Characterizing neoantigens for personalized cancer immunotherapy","volume":"46","author":"A-H Capietto","year":"2017","journal-title":"Curr Opin Immunol"},{"key":"pcbi.1009482.ref013","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1189\/jlb.1113599","article-title":"Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors","volume":"95","author":"LC Ant\u00f3n","year":"2014","journal-title":"J Leukoc Biol"},{"key":"pcbi.1009482.ref014","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.molcel.2018.12.020","article-title":"Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance","volume":"73","author":"J Wei","year":"2019","journal-title":"Mol Cell"},{"key":"pcbi.1009482.ref015","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.4049\/jimmunol.157.5.1823","article-title":"Defective ribosomal products (DRiPs): a major source of antigenic peptides for MHC class I molecules?","volume":"157","author":"JW Yewdell","year":"1996","journal-title":"J Immunol"},{"key":"pcbi.1009482.ref016","doi-asserted-by":"crossref","first-page":"e1003129","DOI":"10.1371\/journal.ppat.1003129","article-title":"Kinetics of Antigen Expression and Epitope Presentation during Virus Infection","volume":"9","author":"NP Croft","year":"2013","journal-title":"PLOS Pathog."},{"key":"pcbi.1009482.ref017","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1074\/mcp.M500241-MCP200","article-title":"The Turnover Kinetics of Major Histocompatibility Complex Peptides of Human Cancer Cells*","volume":"5","author":"E Milner","year":"2006","journal-title":"Mol Cell Proteomics"},{"key":"pcbi.1009482.ref018","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1074\/mcp.M112.024810","article-title":"The Human Leukocyte Antigen\u2013presented Ligandome of B Lymphocytes*","volume":"12","author":"C Hassan","year":"2013","journal-title":"Mol Cell Proteomics"},{"key":"pcbi.1009482.ref019","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1172\/JCI88590","article-title":"MHC class I\u2013associated peptides derive from selective regions of the human genome","volume":"126","author":"H Pearson","year":"2016","journal-title":"J Clin Invest"},{"key":"pcbi.1009482.ref020","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cell.2010.02.036","article-title":"A Role for Codon Order in Translation Dynamics","volume":"141","author":"G Cannarozzi","year":"2010","journal-title":"Cell"},{"key":"pcbi.1009482.ref021","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrg2899","article-title":"Synonymous but not the same: the causes and consequences of codon bias","volume":"12","author":"JB Plotkin","year":"2011","journal-title":"Nat Rev Genet"},{"key":"pcbi.1009482.ref022","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1038\/leu.2016.22","article-title":"Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers","volume":"30","author":"DP Granados","year":"2016","journal-title":"Leukemia"},{"key":"pcbi.1009482.ref023","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.8251.1","article-title":"pyGeno: A Python package for precision medicine and proteogenomics","volume":"5","author":"T Daouda","year":"2016","journal-title":"F1000Research"},{"key":"pcbi.1009482.ref024","doi-asserted-by":"crossref","first-page":"e49708","DOI":"10.7554\/eLife.49708","article-title":"GC content shapes mRNA storage and decay in human cells","volume":"8","author":"M Courel","year":"2019","journal-title":"eLife"},{"key":"pcbi.1009482.ref025","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s002390010219","article-title":"Codon Usage and tRNA Genes in Eukaryotes: Correlation of Codon Usage Diversity with Translation Efficiency and with CG-Dinucleotide Usage as Assessed by Multivariate Analysis","volume":"53","author":"S Kanaya","year":"2001","journal-title":"J Mol Evol"},{"key":"pcbi.1009482.ref026","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrm.2017.91","article-title":"Codon optimality, bias and usage in translation and mRNA decay","volume":"19","author":"G Hanson","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pcbi.1009482.ref027","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1093\/nar\/gkq009","article-title":"Translation efficiency in humans: tissue specificity, global optimization and differences between developmental stages","volume":"38","author":"YY Waldman","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009482.ref028","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1021\/acs.jproteome.6b00971","article-title":"MHC-I Ligand Discovery Using Targeted Database Searches of Mass Spectrometry Data: Implications for T-Cell Immunotherapies","volume":"16","author":"JP Murphy","year":"2017","journal-title":"J Proteome Res"},{"key":"pcbi.1009482.ref029","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aau5516","article-title":"Noncoding regions are the main source of targetable tumor-specific antigens","volume":"10","author":"CM Laumont","year":"2018","journal-title":"Sci Transl Med"},{"key":"pcbi.1009482.ref030","doi-asserted-by":"crossref","first-page":"e1007757","DOI":"10.1371\/journal.pcbi.1007757","article-title":"Benchmarking predictions of MHC class I restricted T cell epitopes in a comprehensively studied model system","volume":"16","author":"S Paul","year":"2020","journal-title":"PLOS Comput Biol"},{"key":"pcbi.1009482.ref031","article-title":"Evaluation: from precision, recall and F-measure to ROC, informedness, markedness and correlation","author":"DMW Powers","year":"2020","journal-title":"ArXiv201016061 Cs Stat"},{"key":"pcbi.1009482.ref032","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-1-4939-9450-2_9","volume-title":"Antigen Processing: Methods and Protocols","author":"D Dersh","year":"2019"},{"key":"pcbi.1009482.ref033","doi-asserted-by":"crossref","first-page":"e18556","DOI":"10.1371\/journal.pone.0018556","article-title":"High Cleavage Efficiency of a 2A Peptide Derived from Porcine Teschovirus-1 in Human Cell Lines, Zebrafish and Mice","volume":"6","author":"JH Kim","year":"2011","journal-title":"PLOS ONE"},{"key":"pcbi.1009482.ref034","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.4049\/jimmunol.150.7.2724","article-title":"Endogenous generation and presentation of the ovalbumin peptide\/Kb complex to T cells","volume":"150","author":"N Shastri","year":"1993","journal-title":"J Immunol"},{"key":"pcbi.1009482.ref035","doi-asserted-by":"crossref","first-page":"10238","DOI":"10.1038\/ncomms10238","article-title":"Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames","volume":"7","author":"CM Laumont","year":"2016","journal-title":"Nat Commun"},{"key":"pcbi.1009482.ref036","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.4049\/jimmunol.1900070","article-title":"Influenza A Virus Infection Induces Viral and Cellular Defective Ribosomal Products Encoded by Alternative Reading Frames","volume":"202","author":"DJ Zanker","year":"2019","journal-title":"J Immunol"},{"key":"pcbi.1009482.ref037","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13073-019-0642-x","article-title":"Discovery and characterization of actionable tumor antigens","volume":"11","author":"G Ehx","year":"2019","journal-title":"Genome Med"},{"key":"pcbi.1009482.ref038","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0952-7915(03)00083-9","article-title":"Epitope-based vaccines: an update on epitope identification, vaccine design and delivery","volume":"15","author":"A Sette","year":"2003","journal-title":"Curr Opin Immunol"},{"key":"pcbi.1009482.ref039","first-page":"1137","article-title":"A neural probabilistic language model","volume":"3","author":"Y Bengio","year":"2003","journal-title":"J Mach Learn Res"},{"key":"pcbi.1009482.ref040","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature14539","article-title":"Deep learning","volume":"521","author":"Y LeCun","year":"2015","journal-title":"Nature"},{"key":"pcbi.1009482.ref041","author":"T. Daouda","year":"2015","journal-title":"Mariana: The Cutest Deep learning Framework"},{"key":"pcbi.1009482.ref042","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nmeth.1318","article-title":"Enzymatic assembly of DNA molecules up to several hundred kilobases","volume":"6","author":"DG Gibson","year":"2009","journal-title":"Nat Methods"},{"key":"pcbi.1009482.ref043","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1074\/mcp.M112.025775","article-title":"Quantitative Proteomics Reveals the Induction of Mitophagy in Tumor Necrosis Factor-\u03b1-activated (TNF\u03b1) Macrophages*","volume":"12","author":"C Bell","year":"2013","journal-title":"Mol Cell Proteomics"},{"key":"pcbi.1009482.ref044","doi-asserted-by":"crossref","first-page":"6020","DOI":"10.1073\/pnas.89.13.6020","article-title":"Detection of rare antigen-presenting cells by the lacZ T-cell activation assay suggests an expression cloning strategy for T-cell antigens","volume":"89","author":"J Karttunen","year":"1992","journal-title":"Proc Natl Acad Sci"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1009482","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T07:48:58Z","timestamp":1673596138000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009482"}},"subtitle":[],"editor":[{"given":"Marco","family":"Punta","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1009482","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]}}}