[en] MHC-I-associated peptides deriving from non-coding genomic regions and mutations can generate tumor-specific antigens, including neoantigens. Quantifying tumor-specific antigens' RNA expression in malignant and benign tissues is critical for discriminating actionable targets. We present BamQuery, a tool attributing an exhaustive RNA expression to MHC-I-associated peptides of any origin from bulk and single-cell RNA-sequencing data. We show that many cryptic and mutated tumor-specific antigens can derive from multiple discrete genomic regions, abundantly expressed in normal tissues. BamQuery can also be used to predict MHC-I-associated peptides immunogenicity and identify actionable tumor-specific antigens de novo.
Disciplines :
Genetics & genetic processes
Author, co-author :
Cuevas, Maria Virginia Ruiz; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada ; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC, H3C 3J7, Canada
Hardy, Marie-Pierre; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada
Larouche, Jean-David; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada ; Department of Medicine, Université de Montréal, Montreal, QC, H3C 3J7, Canada
Apavaloaei, Anca; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada ; Department of Medicine, Université de Montréal, Montreal, QC, H3C 3J7, Canada
Kina, Eralda; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada ; Department of Medicine, Université de Montréal, Montreal, QC, H3C 3J7, Canada
Vincent, Krystel; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada
Gendron, Patrick; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada
Laverdure, Jean-Philippe; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada
Durette, Chantal; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada
Thibault, Pierre ✱; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada ; Department of Chemistry, Université de Montréal, Montreal, QC, H3C 3J7, Canada
Lemieux, Sébastien ✱; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada ; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, QC, H3C 3J7, Canada
Perreault, Claude ✱; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, QC, H3C 3J7, Canada ; Department of Medicine, Université de Montréal, Montreal, QC, H3C 3J7, Canada
Ehx, Grégory ✱; Université de Liège - ULiège > Département des sciences cliniques
Canadian Cancer Society [CA] CIHR - Canadian Institutes of Health Research [CA]
Funding text :
We are grateful to Qingchuan Zhao, Assya Trofimov, Nandita Noronha, and Caroline Labelle for valuable biological insights, suggestions, and testing BamQuery. We also thank all other members of our laboratories for their thoughtful recommendations. We thank Eric Audemard and Geneviève Boucher of the IRIC bioinformatic platform for assistance with bioinformatics tools. We thank the Genotype-Tissue Expression (GTEx) Project for providing RNA-seq data. The GTEx Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS.This study was supported by grants from the Canadian Cancer Society (707264), and the Canadian Institutes of Health Research (FDN 148400). The Perreault lab is supported in part by the Katelyn Bedard Bone Marrow Association and the Fonds Vaccins Thérapeutiques Contre le Cancer. GE is supported by post-doctoral fellowships from the IRIC, FRQS, The Cole Foundation, and the F.R.S.-FNRS. This study was also supported by the “Promouvoir la Recherche” foundation, Leon Fredericq foundation, and the Fund Suzanne Duschene & the Fund Serge Rousseau, managed by the King Baudouin Foundation.
Pishesha N, Harmand TJ, Ploegh HL. A guide to antigen processing and presentation. Nat Rev Immunol. 2022;22:751–64.
Lang F, Schrörs B, Löwer M, Türeci Ö, Sahin U. Identification of neoantigens for individualized therapeutic cancer vaccines. Nat Rev Drug Discov. 2022;21:261–82.
Chong C, Coukos G, Bassani-Sternberg M. Identification of tumor antigens with immunopeptidomics. Nat Biotechnol. 2022;40:175–88.
Laumont CM, Daouda T, Laverdure JP, Bonneil E, Caron-Lizotte O, Hardy MP, Granados DP, Durette C, Lemieux S, Thibault P, Perreault C. Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames. Nat Commun. 2016;7:10238.
Ruiz Cuevas MV, Hardy MP, Holly J, Bonneil E, Durette C, Courcelles M, Lanoix J, Cote C, Staudt LM, Lemieux S, et al. Most non-canonical proteins uniquely populate the proteome or immunopeptidome. Cell Rep. 2021;34: 108815.
Erhard F, Halenius A, Zimmermann C, L’Hernault A, Kowalewski DJ, Weekes MP, Stevanovic S, Zimmer R, Dölken L. Improved Ribo-seq enables identification of cryptic translation events. Nat Methods. 2018;15:363–6.
Guilloy N, Brunet MA, Leblanc S, Jacques JF, Hardy MP, Ehx G, Lanoix J, Thibault P, Perreault C, Roucou X. OpenCustomDB: integration of unannotated open reading frames and genetic variants to generate more comprehensive customized protein databases. J Proteome Res. 2023;22:1492–500.
Chong C, Muller M, Pak H, Harnett D, Huber F, Grun D, Leleu M, Auger A, Arnaud M, Stevenson BJ, et al. Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes. Nat Commun. 2020;11:1293.
Laumont CM, Vincent K, Hesnard L, Audemard E, Bonneil E, Laverdure JP, Gendron P, Courcelles M, Hardy MP, Cote C, Noncoding regions are the main source of targetable tumor-specific antigens. Sci Transl Med. 2018;10.
Zhao Q, Laverdure JP, Lanoix J, Durette C, Cote C, Bonneil E, Laumont CM, Gendron P, Vincent K, Courcelles M, et al. Proteogenomics Uncovers a Vast Repertoire of Shared Tumor-Specific Antigens in Ovarian Cancer. Cancer Immunol Res. 2020;8:544–55.
Apavaloaei A, Hesnard L, Hardy MP, Benabdallah B, Ehx G, Thériault C, Laverdure JP, Durette C, Lanoix J, Courcelles M, et al. Induced pluripotent stem cells display a distinct set of MHC I-associated peptides shared by human cancers. Cell Rep. 2022;40: 111241.
Gee MH, Han A, Lofgren SM, Beausang JF, Mendoza JL, Birnbaum ME, Bethune MT, Fischer S, Yang X, Gomez-Eerland R, et al. Antigen identification for orphan T cell receptors expressed on tumor-infiltrating lymphocytes. Cell. 2018;172:549-563.e516.
Probst P, Kopp J, Oxenius A, Colombo MP, Ritz D, Fugmann T, Neri D. Sarcoma eradication by doxorubicin and targeted TNF relies upon CD8(+) T-cell recognition of a retroviral antigen. Cancer Res. 2017;77:3644–54.
Putri GH, Anders S, Pyl PT, Pimanda JE, Zanini F: Analysing high-throughput sequencing data in Python with HTSeq 2.0. Bioinformatics. 2022;38:2943–2945.
Ehx G, Perreault C. Discovery and characterization of actionable tumor antigens. Genome Medicine. 2019;11:29.
Pearson H, Daouda T, Granados DP, Durette C, Bonneil E, Courcelles M, Rodenbrock A, Laverdure JP, Cote C, Mader S, et al. MHC class I-associated peptides derive from selective regions of the human genome. J Clin Invest. 2016;126:4690–701.
Takahama Y, Ohigashi I, Baik S, Anderson G. Generation of diversity in thymic epithelial cells. Nat Rev Immunol. 2017;17:295–305.
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.
Smigielski EM, Sirotkin K, Ward M, Sherry ST. dbSNP: a database of single nucleotide polymorphisms. Nucleic Acids Res. 2000;28:352–5.
Marcu A, Bichmann L, Kuchenbecker L, Kowalewski DJ, Freudenmann LK, Backert L, Mühlenbruch L, Szolek A, Lübke M, Wagner P, et al. HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy. J Immunother Cancer. 2021;9.
Larouche JD, Trofimov A, Hesnard L, Ehx G, Zhao Q, Vincent K, Durette C, Gendron P, Laverdure JP, Bonneil E, et al. Widespread and tissue-specific expression of endogenous retroelements in human somatic tissues. Genome Med. 2020;12:40.
Marcais G, Kingsford C. A fast, lock-free approach for efficient parallel counting of occurrences of k-mers. Bioinformatics. 2011;27:764–70.
Ballouz S, Dobin A, Gingeras TR, Gillis J. The fractured landscape of RNA-seq alignment: the default in our STARs. Nucleic Acids Res. 2018;46:5125–38.
Liu X, Zhao J, Xue L, Zhao T, Ding W, Han Y, Ye H. A comparison of transcriptome analysis methods with reference genome. BMC Genomics. 2022;23:232.
Granados DP, Rodenbrock A, Laverdure JP, Cote C, Caron-Lizotte O, Carli C, Pearson H, Janelle V, Durette C, Bonneil E, et al. Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers. Leukemia. 2016;30:1344–54.
Bassani-Sternberg M, Pletscher-Frankild S, Jensen LJ, Mann M. Mass spectrometry of human leukocyte antigen class I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation. Mol Cell Proteomics. 2015;14:658–73.
Zhang H, Liu T, Zhang Z, Payne SH, Zhang B, McDermott JE, Zhou JY, Petyuk VA, Chen L, Ray D, et al. Integrated proteogenomic characterization of human high-grade serous ovarian cancer. Cell. 2016;166:755–65.
Fergusson JR, Morgan MD, Bruchard M, Huitema L, Heesters BA, van Unen V, van Hamburg JP, van der Wel NN, Picavet D, Koning F, et al. Maturing human CD127+ CCR7+ PDL1+ dendritic cells express AIRE in the absence of tissue restricted antigens. Front Immunol. 2018;9:2902.
GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45:580-585.
Varenne S, Buc J, Lloubes R, Lazdunski C. Translation is a non-uniform process. Effect of tRNA availability on the rate of elongation of nascent polypeptide chains. J Mol Biol. 1984;180:549–576.
Sørensen MA, Kurland CG, Pedersen S. Codon usage determines translation rate in Escherichia coli. J Mol Biol. 1989;207:365–77.
Yu CH, Dang Y, Zhou Z, Wu C, Zhao F, Sachs MS, Liu Y. Codon usage influences the local rate of translation elongation to regulate co-translational protein folding. Mol Cell. 2015;59:744–54.
Yewdell JW, Hollý J. DRiPs get molecular. Curr Opin Immunol. 2020;64:130–6.
Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell. 2015;161:1202–14.
Picelli S, Bjorklund AK, Faridani OR, Sagasser S, Winberg G, Sandberg R. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat Methods. 2013;10:1096–8.
Lambrechts D, Wauters E, Boeckx B, Aibar S, Nittner D, Burton O, Bassez A, Decaluwe H, Pircher A, Van den Eynde K, et al. Phenotype molding of stromal cells in the lung tumor microenvironment. Nat Med. 2018;24:1277–89.
Madissoon E, Wilbrey-Clark A, Miragaia RJ, Saeb-Parsy K, Mahbubani KT, Georgakopoulos N, Harding P, Polanski K, Huang N, Nowicki-Osuch K, et al. scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation. Genome Biol. 2019;21:1.
Petti AA, Williams SR, Miller CA, Fiddes IT, Srivatsan SN, Chen DY, Fronick CC, Fulton RS, Church DM, Ley TJ. A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing. Nat Commun. 2019;10:3660.
La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H, Petukhov V, Lidschreiber K, Kastriti ME, Lönnerberg P, Furlan A, et al. RNA velocity of single cells. Nature. 2018;560:494–8.
Patrick R, Humphreys DT, Janbandhu V, Oshlack A, Ho JWK, Harvey RP, Lo KK. Sierra: discovery of differential transcript usage from polyA-captured single-cell RNA-seq data. Genome Biol. 2020;21:167.
Choi K, Chen Y, Skelly DA, Churchill GA. Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics. Genome Biol. 2020;21:183.
Finak G, McDavid A, Yajima M, Deng J, Gersuk V, Shalek AK, Slichter CK, Miller HW, McElrath MJ, Prlic M, et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 2015;16:278.
Tan X, Li D, Huang P, Jian X, Wan H, Wang G, Li Y, Ouyang J, Lin Y, Xie L. dbPepNeo: a manually curated database for human tumor neoantigen peptides. Database (Oxford). 2020;2020.
Xia J, Bai P, Fan W, Li Q, Li Y, Wang D, Yin L, Zhou Y. NEPdb: a database of T-cell experimentally-validated neoantigens and pan-cancer predicted neoepitopes for cancer immunotherapy. Front Immunol. 2021;12: 644637.
Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015;348:803–808.
Hirama T, Tokita S, Nakatsugawa M, Murata K, Nannya Y, Matsuo K, Inoko H, Hirohashi Y, Hashimoto S, Ogawa S, et al. Proteogenomic identification of an immunogenic HLA class I neoantigen in mismatch repair-deficient colorectal cancer tissue. JCI Insight. 2021;6.
Choi J, Baldwin TM, Wong M, Bolden JE, Fairfax KA, Lucas EC, Cole R, Biben C, Morgan C, Ramsay KA, et al. Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans. Nucleic Acids Res. 2019;47:D780-d785.
Silvin A, Yu CI, Lahaye X, Imperatore F, Brault JB, Cardinaud S, Becker C, Kwan WH, Conrad C, Maurin M, et al. Constitutive resistance to viral infection in human CD141(+) dendritic cells. Sci Immunol. 2017;2.
Rivero-Hinojosa S, Grant M, Panigrahi A, Zhang H, Caisova V, Bollard CM, Rood BR. Proteogenomic discovery of neoantigens facilitates personalized multi-antigen targeted T cell immunotherapy for brain tumors. Nat Commun. 2021;12:6689.
Bonaventura P, Alcazer V, Mutez V, Tonon L, Martin J, Chuvin N, Michel E, Boulos RE, Estornes Y, Valladeau-Guilemond J, Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy. Sci Adv. 2022;8:eabj3671.
Liepe J, Marino F, Sidney J, Jeko A, Bunting DE, Sette A, Kloetzel PM, Stumpf MP, Heck AJ, Mishto M. A large fraction of HLA class I ligands are proteasome-generated spliced peptides. Science. 2016;354:354–8.
Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, Elledge SJ, Niebuhr DW, Scher AI, Munger KL, Ascherio A. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022;375:296–301.
Tsang ML, Münz C. Cytolytic T lymphocytes from HLA-B8+ donors frequently recognize the Hodgkin’s lymphoma associated latent membrane protein 2 of Epstein Barr virus. Herpesviridae. 2011;2:4.
Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, Kammula US, Royal RE, Sherry RM, Wunderlich JR, et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood. 2009;114:535–46.
Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA, Feldman SA, Davis JL, Morgan RA, Merino MJ, Sherry RM, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther. 2011;19:620–6.
Cameron BJ, Gerry AB, Dukes J, Harper JV, Kannan V, Bianchi FC, Grand F, Brewer JE, Gupta M, Plesa G, Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci Transl Med. 2013;5:197ra103.
van Amerongen RA, Morton LT, Chaudhari UG, Remst DFG, Hagedoorn RS, van den Berg CW, Freund C, Falkenburg JHF, Heemskerk MHM. Human iPSC-derived preclinical models to identify toxicity of tumor-specific T cells with clinical potential. Mol Ther Methods Clin Dev. 2023;28:249–61.
Ishihara M, Tono Y, Miyahara Y, Muraoka D, Harada N, Kageyama S, Sasaki T, Hori Y, Soga N, Uchida K, et al. First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors. Cancer Immunol Immunother. 2020;69:663–75.
Ishihara M, Kitano S, Kageyama S, Miyahara Y, Yamamoto N, Kato H, Mishima H, Hattori H, Funakoshi T, Kojima T, et al. NY-ESO-1-specific redirected T cells with endogenous TCR knockdown mediate tumor response and cytokine release syndrome. J Immunother Cancer. 2022;10.
Xia Y, Tian X, Wang J, Qiao D, Liu X, Xiao L, Liang W, Ban D, Chu J, Yu J, et al. Treatment of metastatic non-small cell lung cancer with NY-ESO-1 specific TCR engineered-T cells in a phase I clinical trial: a case report. Oncol Lett. 2018;16:6998–7007.
Rohaan MW, Gomez-Eerland R, van den Berg JH, Geukes Foppen MH, van Zon M, Raud B, Jedema I, Scheij S, de Boer R, Bakker NAM, et al. MART-1 TCR gene-modified peripheral blood T cells for the treatment of metastatic melanoma: a phase I/IIa clinical trial. Immunooncol Technol. 2022;15: 100089.
Yee C, Thompson JA, Roche P, Byrd DR, Lee PP, Piepkorn M, Kenyon K, Davis MM, Riddell SR, Greenberg PD. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo. J Exp Med. 2000;192:1637–44.
van den Berg JH, Gomez-Eerland R, van de Wiel B, Hulshoff L, van den Broek D, Bins A, Tan HL, Harper JV, Hassan NJ, Jakobsen BK, et al. Case report of a fatal serious adverse event upon administration of T cells transduced with a MART-1-specific T-cell receptor. Mol Ther. 2015;23:1541–50.
Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, et al. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother. 2013;36:133–51.
Park J, Talukder AH, Lim SA, Kim K, Pan K, Melendez B, Bradley SD, Jackson KR, Khalili JS, Wang J, et al. SLC45A2: a melanoma antigen with high tumor selectivity and reduced potential for autoimmune toxicity. Cancer Immunol Res. 2017;5:618–29.
Kageyama S, Ikeda H, Miyahara Y, Imai N, Ishihara M, Saito K, Sugino S, Ueda S, Ishikawa T, Kokura S, et al. Adoptive transfer of MAGE-A4 T-cell receptor gene-transduced lymphocytes in patients with recurrent esophageal cancer. Clin Cancer Res. 2015;21:2268–77.
Vonderheide RH, Domchek SM, Schultze JL, George DJ, Hoar KM, Chen DY, Stephans KF, Masutomi K, Loda M, Xia Z, et al. Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res. 2004;10:828–39.
Dreno B, Thompson JF, Smithers BM, Santinami M, Jouary T, Gutzmer R, Levchenko E, Rutkowski P, Grob JJ, Korovin S, et al. MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage III melanoma (DERMA): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19:916–29.
Atanackovic D, Altorki NK, Stockert E, Williamson B, Jungbluth AA, Ritter E, Santiago D, Ferrara CA, Matsuo M, Selvakumar A, et al. Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients. J Immunol. 2004;172:3289–96.
Pol JG, Acuna SA, Yadollahi B, Tang N, Stephenson KB, Atherton MJ, Hanwell D, El-Warrak A, Goldstein A, Moloo B, et al. Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials. Oncoimmunology. 2019;8: e1512329.
Pabst C, Bergeron A, Lavallee VP, Yeh J, Gendron P, Norddahl GL, Krosl J, Boivin I, Deneault E, Simard J, et al. GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo. Blood. 2016;127:2018–27.
Almeida LG, Sakabe NJ, deOliveira AR, Silva MC, Mundstein AS, Cohen T, Chen YT, Chua R, Gurung S, Gnjatic S, et al. CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens. Nucleic Acids Res. 2009;37:D816-819.
Ogishi M, Yotsuyanagi H. Quantitative prediction of the landscape of T cell epitope immunogenicity in sequence space. Front Immunol. 2019;10:827.
Adamopoulou E, Tenzer S, Hillen N, Klug P, Rota IA, Tietz S, Gebhardt M, Stevanovic S, Schild H, Tolosa E, et al. Exploring the MHC-peptide matrix of central tolerance in the human thymus. Nat Commun. 2013;4:2039.
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–8.
Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, et al. COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res. 2018;47:D941–7.
Rattay K, Meyer HV, Herrmann C, Brors B, Kyewski B. Evolutionary conserved gene co-expression drives generation of self-antigen diversity in medullary thymic epithelial cells. J Autoimmun. 2016;67:65–75.
Kadouri N, Nevo S, Goldfarb Y, Abramson J. Thymic epithelial cell heterogeneity: TEC by TEC. Nat Rev Immunol. 2020;20:239–53.
Audiger C, Rahman MJ, Yun TJ, Tarbell KV, Lesage S. The importance of dendritic cells in maintaining immune tolerance. J Immunol. 2017;198:2223–31.
Arnaud M, Chiffelle J, Genolet R, Navarro Rodrigo B, Perez MAS, Huber F, Magnin M, Nguyen-Ngoc T, Guillaume P, Baumgaertner P, et al. Sensitive identification of neoantigens and cognate TCRs in human solid tumors. Nat Biotechnol. 2022;40:656–60.
Ouspenskaia T, Law T, Clauser KR, Klaeger S, Sarkizova S, Aguet F, Li B, Christian E, Knisbacher BA, Le PM, et al. Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer. Nat Biotechnol. 2022;40:209–17.
Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, et al. Landscape of transcription in human cells. Nature. 2012;489:101–8.
Smart AC, Margolis CA, Pimentel H, He MX, Miao D, Adeegbe D, Fugmann T, Wong K-K, Van Allen EM. Intron retention is a source of neoepitopes in cancer. Nat Biotechnol. 2018;36:1056–8.
Welters MJ, Kenter GG, Piersma SJ, Vloon AP, Löwik MJ, Berends-van der Meer DM, Drijfhout JW, Valentijn AR, Wafelman AR, Oostendorp J,. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin Cancer Res. 2008;14:178–187.
Ruiz-Cuevas MV, Ehx G. BamQuery: a proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens. California: Github; 2022.
Ruiz-Cuevas MV, Ehx G. BamQuery: a proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens. Switzerland: Zenodo; 2022.
Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R. Genome Project Data Processing S: The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25:2078–9.
Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26:841–2.
Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, Lee MJ, Wilk AJ, Darby C, Zager M, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184(3573–3587): e3529.
Noronha N, Ehx G, Meunier MC, Laverdure JP, Thériault C, Perreault C. Major multilevel molecular divergence between THP-1 cells from different biorepositories. Int J Cancer. 2020;147:2000–6.
Laumont CM, Vincent K, Hesnard L, Audemard É, Bonneil É, Laverdure JP, Gendron P, Courcelles M, Hardy MP, Côté C, Durette C, St-Pierre C, Benhammadi M, Lanoix J, Vobecky S, Haddad E, Lemieux S, Thibault P, Perreault C. Gene Expression Omnibus. 2018. https://identifiers.org/geo:GSE127825.
Larouche JD, Trofimov A, Hesnard L, Ehx G, Zhao Q, Vincent K, Durette C, Gendron P, Laverdure JP, Bonneil É, Côté C, Lemieux S, Thibault P, Perreault C. Gene Expression Omnibus. 2019. https://identifiers.org/geo:GSE127826.
Fergusson JR, Morgan MD, Bruchard M, Huitema L, Heesters BA, van Unen V, van Hamburg JP, van der Wel NN, Picavet D, Koning F, Tas SW, Anderson MS, Marioni JC, Holländer GA, Spits H. ArrayExpress. 2019. https://identifiers.org/ArrayExpress:E-MTAB-7383.
Ehx G, Larouche JD, Durette C, Laverdure JP, Hesnard L, Vincent K, Hardy MP, Thériault C, Rulleau C, Lanoix J, Bonneil E, Feghaly A, Apavaloaei A, Noronha N, Laumont CM, Delisle JS, Vago L, Hébert J, Sauvageau G, Lemieux S, Thibault P, Perreault C. Gene Expression Omnibus. 2021. https://identifiers.org/geo:GSE147524.
Ehx G, Larouche JD, Durette C, Laverdure JP, Hesnard L, Vincent K, Hardy MP, Thériault C, Rulleau C, Lanoix J, Bonneil E, Feghaly A, Apavaloaei A, Noronha N, Laumont CM, Delisle JS, Vago L, Hébert J, Sauvageau G, Lemieux S, Thibault P, Perreault C. PRIDE. 2021. https://identifiers.org/PRIDE:PXD018542.
Ruiz Cuevas MV, Hardy MP, Hollý J, Bonneil É, Durette C, Courcelles M, Lanoix J, Côté C, Staudt LM, Lemieux S, Thibault P, Perreault C, Yewdell JW. BioProject. 2021. https://identifiers.org/BioProject:PRJNA647736.
Ruiz Cuevas MV, Hardy MP, Hollý J, Bonneil É, Durette C, Courcelles M, Lanoix J, Côté C, Staudt LM, Lemieux S, Thibault P, Perreault C, Yewdell JW. PRIDE. 2021. https://identifiers.org/PRIDE:PXD020620.
Madissoon E, Wilbrey-Clark A, Miragaia RJ, Saeb-Parsy K, Mahbubani KT, Georgakopoulos N, Harding P, Polanski K, Huang N, Nowicki-Osuch K, Fitzgerald RC, Loudon KW, Ferdinand JR, Clatworthy MR, Tsingene A, van Dongen S, Dabrowska M, Patel M, Stubbington MJT, Teichmann SA, Stegle O, Meyer KB. BioProject. 2019. https://identifiers.org/BioProject:PRJEB31843.
Lambrechts D, Wauters E, Boeckx B, Aibar S, Nittner D, Burton O, Bassez A, Decaluwé H, Pircher A, Van den Eynde K, Weynand B, Verbeken E, De Leyn P, Liston A, Vansteenkiste J, Carmeliet P, Aerts S, Thienpont B. ArrayExpress. 2018. https://identifiers.org/ArrayExpress:E-MTAB-6653.
Choi J, Baldwin TM, Wong M, Bolden JE, Fairfax KA, Lucas EC, Cole R, Biben C, Morgan C, Ramsay KA, Ng AP, Kauppi M, Corcoran LM, Shi W, Wilson N, Wilson MJ, Alexander WS, Hilton DJ, de Graaf CA. Gene Expression Omnibus. 2019. https://identifiers.org/geo:GSE115736.
Silvin A, Yu IC, Lahaye X, Imperatore F, Brault JB, Cardinaud S, Becker C, Kwan WH, Conrad C, Maurin M, Goudot C, Marques-Ladeira S, Wang Y, Pascual V, Anguiano E, Albrecht RA, Iannacone M, García-Sastre A, Goud B, Dalod M, Moris A, Merad M, Palucka AK, Manel N. Gene Expression Omnibus. 2017. https://identifiers.org/geo:GSE76511.
Network Cancer Genome Atlas. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.
