{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:24:55Z","timestamp":1778577895604,"version":"3.51.4"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Over the last years, great efforts have been devoted to develop effective gluten detoxification strategies with a consequent detrimental alteration of the technological properties as well. Obtaining low-gluten products without affecting the rheological properties of wheat could still be considered a new challenge to face. In this investigation, we presented a comprehensive characterization of durum wheat genotypes aimed at identifying low gluten ones, which combine the potential lower toxicity\/immunogenicity with conserved yield and rheological properties to encompass the perspective usability for bread or pasta making. A preliminary profiling of gluten proteins was accomplished by immunoassay-based quantification and liquid chromatography coupled to UV detection, focusing on the gliadin fraction as main responsible for immunoreactivity in celiac disease patients. In addition, data on grain protein content, grain yield per spike, dry gluten and gluten index were collected in order to provide complementary information about productivity-related traits and quali-quantitative characteristics related to wheat nutritional value and its technological properties. The whole pool of data was statistically evaluated driving to the selection of a preferred list of candidate low-toxicity genotypes that were subjected to <jats:italic>in-vitro<\/jats:italic> simulated gastroduodenal digestion and untargeted HR-MS\/MS peptide identification. Finally, an in-silico risk assessment of potential toxicity for celiac disease patients was performed according to the most recent guidance provided by EFSA.<\/jats:p>","DOI":"10.1038\/s41598-018-36845-8","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T11:05:41Z","timestamp":1549537541000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Scouting for Naturally Low-Toxicity Wheat Genotypes by a Multidisciplinary Approach"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6789-1472","authenticated-orcid":false,"given":"Rosa","family":"Pilolli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata","family":"Gadaleta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Mamone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenica","family":"Nigro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"De Angelis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Montemurro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Monaci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,2,7]]},"reference":[{"key":"36845_CR1","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1080\/07853890.2017.1325968","volume":"49","author":"S Valenti","year":"2017","unstructured":"Valenti, S., Corica, D., Ricciardi, L. & Romano, C. Gluten-related disorders: certainties, questions and dounts. Ann. Med. 49, 569\u2013581 (2017).","journal-title":"Ann. Med."},{"key":"36845_CR2","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1001\/jama.2017.9730","volume":"318","author":"MM Leonard","year":"2017","unstructured":"Leonard, M. M., Sapone, A., Catassi, C. & Fasano, A. Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA. 318, 647\u2013656 (2017).","journal-title":"JAMA."},{"key":"36845_CR3","first-page":"82","volume":"14","author":"B Niland","year":"2018","unstructured":"Niland, B. & Cash, B. D. Health benefits and adverse effects of a gluten-free diet in non-celiac disease patients. Gastroenerol Hepatol 14, 82\u201391 (2018).","journal-title":"Gastroenerol Hepatol"},{"key":"36845_CR4","doi-asserted-by":"publisher","first-page":"2215","DOI":"10.1007\/s10620-017-4649-0","volume":"62","author":"L Emilsson","year":"2017","unstructured":"Emilsson, L. & Semrad, C. E. Obesity, Metabolic Syndrome, and Cardiac Risk Factors: Going Gluten-Free, for Better or Worse? Digest Dis Sci 62, 2215\u20132216 (2017).","journal-title":"Digest Dis Sci"},{"key":"36845_CR5","doi-asserted-by":"publisher","first-page":"i2716","DOI":"10.1136\/bmj.i2716","volume":"353","author":"D Aune","year":"2016","unstructured":"Aune, D. et al. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specifi mortality: systematic review and dose-response metaanalysis of prospective studies. BMJ 353, i2716 (2016).","journal-title":"BMJ"},{"key":"36845_CR6","doi-asserted-by":"publisher","first-page":"j1892","DOI":"10.1136\/bmj.j1892","volume":"357","author":"B Lebwohl","year":"2017","unstructured":"Lebwohl, B. et al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 357, j1892 (2017).","journal-title":"BMJ"},{"key":"36845_CR7","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.1007\/s10620-017-4583-1","volume":"62","author":"H-S Kim","year":"2017","unstructured":"Kim, H.-S. et al. Obesity, Metabolic Syndrome, and Cardiovascular Risk in Gluten-Free Followers Without Celiac Disease in the United States: Results from the National Health and Nutrition Examination Survey 2009\u20132014. Digest Dis Sci 62, 2440\u20132448 (2017).","journal-title":"Digest Dis Sci"},{"issue":"4","key":"36845_CR8","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1111\/apt.14175","volume":"46","author":"R Mandile","year":"2017","unstructured":"Mandile, R. et al. Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short-term oral challenge. Aliment. Pharmacol. Ther. 46(4), 440\u2013446 (2017).","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"14","key":"36845_CR9","doi-asserted-by":"publisher","first-page":"e00376","DOI":"10.1128\/AEM.00376-17","volume":"83","author":"R Francavilla","year":"2017","unstructured":"Francavilla, R. et al. Selected probiotic lactobacilli have the capacity to hydrolyze gluten peptides during simulated gastrointestinal digestion. Appl Environ Microbiol. 83(14), e00376\u201317 (2017).","journal-title":"Appl Environ Microbiol."},{"issue":"9","key":"36845_CR10","doi-asserted-by":"publisher","first-page":"H2263","DOI":"10.1111\/1750-3841.13410","volume":"81","author":"CG Rizzello","year":"2016","unstructured":"Rizzello, C. G., Montemurro, M. & Gobbetti, M. Characterization of the Bread Made with Durum Wheat Semolina Rendered Gluten Free by Sourdough Biotechnology in Comparison with Commercial Gluten-Free Products. J. Food Sci. 81(9), H2263\u2013H2272 (2016).","journal-title":"J. Food Sci."},{"issue":"14","key":"36845_CR11","doi-asserted-by":"publisher","first-page":"4499","DOI":"10.1128\/AEM.00260-07","volume":"73","author":"CG Rizzello","year":"2007","unstructured":"Rizzello, C. G. et al. Highly efficient gluten degradation by lactobacilli and fungal proteases during food processing: New perspectives for celiac disease. Appl Environ Microbiol. 73(14), 4499\u20134507 (2007).","journal-title":"Appl Environ Microbiol."},{"key":"36845_CR12","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.foodres.2017.04.010","volume":"110","author":"M Gobbetti","year":"2018","unstructured":"Gobbetti, M. et al. How to improve the gluten-free diet: The state of the art from a food science perspective. Food Res Int 110, 22\u201332 (2018).","journal-title":"Food Res Int"},{"key":"36845_CR13","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1111\/1541-4337.12288","volume":"16","author":"F Boukid","year":"2017","unstructured":"Boukid, F., Mejri, M., Pellegrini, N., Sforza, S. & Prandi, B. How Looking for celiac-safe wheat can influence its technological properties. Compr. Rev. Food Sci. F. 16, 797\u2013807 (2017).","journal-title":"Compr. Rev. Food Sci. F."},{"key":"36845_CR14","doi-asserted-by":"publisher","unstructured":"Scherf K. A., Wieser, H. & Koehler, P. Novel approaches for enzymatic gluten degradation to create high-quality gluten-free products. Food Res. Intern. https:\/\/doi.org\/10.1016\/j.foodres.2016.11.021 (2016).","DOI":"10.1016\/j.foodres.2016.11.021"},{"key":"36845_CR15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/1541-4337.12315","volume":"17","author":"F Boukid","year":"2018","unstructured":"Boukid, F., Folloni, S., Sforza, S., Vittadini, E. & Prandi, B. Current Trends in Ancient Grains-Based Foodstuffs: Insights into Nutritional Aspects and Technological Applications. Compr. Rev. Food Sci. F. 17, 123\u2013136 (2018).","journal-title":"Compr. Rev. Food Sci. F."},{"key":"36845_CR16","doi-asserted-by":"publisher","first-page":"161","DOI":"10.2135\/cropsci2008.03.0125","volume":"49","author":"YB Fu","year":"2009","unstructured":"Fu, Y. B. & Somers, D. J. Genome-Wide Reduction of Genetic Diversity in Wheat Breeding. Crop Sci 49, 161\u2013168 (2009).","journal-title":"Crop Sci"},{"key":"36845_CR17","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.clnu.2009.03.013","volume":"28","author":"O Vincentini","year":"2009","unstructured":"Vincentini, O. et al. T-cell response to different cultivars of farro wheat, Triticum turgidum ssp. dicoccum, in celiac disease patients. Clin. Nutr. 28, 272\u2013277 (2009).","journal-title":"Clin. Nutr."},{"key":"36845_CR18","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1039\/c0mb00046a","volume":"6","author":"H van den Broeck","year":"2010","unstructured":"van den Broeck, H. et al. In search of tetraploid wheat accessions reduced in celiac disease-related gluten epitopes. Mol. BioSyst. 6, 2206\u20132213 (2010).","journal-title":"Mol. BioSyst."},{"key":"36845_CR19","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.clnu.2013.02.003","volume":"32","author":"T \u0160uligoj","year":"2013","unstructured":"\u0160uligoj, T., Gregorini, A., Colomba, M., Ellis, H. J. & Ciclitira, P. J. Evaluation of the safety of ancient strains of wheat in coeliac disease reveals heterogeneous small intestinal T cell responses suggestive of coeliac toxicity. Clin. Nutr. 32, 1043\u20131049 (2013).","journal-title":"Clin. Nutr."},{"key":"36845_CR20","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1471-230X-13-92","volume":"13","author":"B Zanini","year":"2013","unstructured":"Zanini, B. et al. Search for atoxic cereals: a single blind, cross-over study on the safety of a single dose of Triticum monococcum, in patients with celiac disease. BMC Gastroenterol. 13, 92 (2013).","journal-title":"BMC Gastroenterol."},{"key":"36845_CR21","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.jcs.2013.10.006","volume":"59","author":"B Prandi","year":"2014","unstructured":"Prandi, B., Mantovani, P., Galaverna, G. & Sforza, S. Genetic and environmental factors affecting pathogenicity of wheat as related to celiac disease. J. Cereal Sci 59, 62\u201369 (2014).","journal-title":"J. Cereal Sci"},{"key":"36845_CR22","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.tifs.2018.02.021","volume":"75","author":"M Ribeiro","year":"2018","unstructured":"Ribeiro, M. et al. Next-generation therapies for celiac disease: The gluten-targeted approaches. Trends Food Sci Tech 75, 56\u201371 (2018).","journal-title":"Trends Food Sci Tech"},{"key":"36845_CR23","first-page":"e4862","volume":"15","author":"H Naegeli","year":"2017","unstructured":"Naegeli, H. et al. EFSA Panel on Genetically Modified Organisms (GMO). EFSA J. 15, e4862\u201349 (2017).","journal-title":"EFSA J."},{"key":"36845_CR24","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1586\/epr.10.98","volume":"8","author":"G Mamone","year":"2011","unstructured":"Mamone, G., Picariello, G., Addeo, F. & Ferranti, P. Proteomic analysis in allergy and intolerance to wheat products. Expert Rev. Proteomics. 8, 95\u2013115 (2011).","journal-title":"Expert Rev. Proteomics."},{"key":"36845_CR25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.foodchem.2016.06.043","volume":"213","author":"M Ribeiro","year":"2016","unstructured":"Ribeiro, M. et al. New insights into wheat toxicity: Breeding did not seem to contribute to a prevalence of potential celiac disease\u2019s immunostimulatory epitopes. Food Chem. 213, 8\u201318 (2016).","journal-title":"Food Chem."},{"key":"36845_CR26","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.eja.2017.04.003","volume":"87","author":"MA De Santis","year":"2017","unstructured":"De Santis, M. A. et al. Differences in gluten protein composition between old and modern durum wheat genotypes in relation to 20th century breeding in Italy. Eur. J. Agron. 87, 19\u201329 (2017).","journal-title":"Eur. J. Agron."},{"key":"36845_CR27","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1080\/09540105.2017.1319342","volume":"28","author":"BV Mohan Kumar","year":"2017","unstructured":"Mohan Kumar, B. V., Prasada Rao, U. J. S. & Prabhasankar, P. Immunogenicity characterization of hexaploid and tetraploid wheat varieties related to celiac disease and wheat allergy. Food Agric. Immunol. 28, 888\u2013903 (2017).","journal-title":"Food Agric. Immunol."},{"key":"36845_CR28","doi-asserted-by":"publisher","unstructured":"Hajas, L. et al. Variation in protein composition among wheat (Triticum aestivum L.) cultivars to identify cultivars suitable as reference material for wheat gluten analysis. Food Chem. https:\/\/doi.org\/10.1016\/j.foodchem.2017.05.005 (2017).","DOI":"10.1016\/j.foodchem.2017.05.005"},{"key":"36845_CR29","doi-asserted-by":"publisher","first-page":"5837","DOI":"10.1021\/acs.jafc.7b02041","volume":"65","author":"F Boukid","year":"2017","unstructured":"Boukid, F. et al. Understanding the Effects of Genotype, Growing Year, and Breeding on Tunisian Durum Wheat Allergenicity. 2. The Celiac Disease Case. J. Agric. Food Chem. 65, 5837\u20135846 (2017).","journal-title":"J. Agric. Food Chem."},{"key":"36845_CR30","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.foodres.2016.11.034","volume":"91","author":"B Prandi","year":"2017","unstructured":"Prandi, B., Tedeschi, T., Folloni, S., Galaverna, G. & Sforza, S. Peptides from gluten digestion: A comparison between old and modern wheat varieties. Food Res. Int. 91, 92\u2013102 (2017).","journal-title":"Food Res. Int."},{"key":"36845_CR31","doi-asserted-by":"publisher","first-page":"4765","DOI":"10.1007\/s00216-014-7858-9","volume":"406","author":"B Prandi","year":"2014","unstructured":"Prandi, B. et al. Qualitative and quantitative determination of peptides related to celiac disease in mixtures derived from different methods of simulated gastrointestinal digestion of wheat products. Anal. Bioanal. Chem. 406, 4765\u20134775 (2014).","journal-title":"Anal. Bioanal. Chem."},{"key":"36845_CR32","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1002\/mnfr.201500126","volume":"59","author":"C Gianfrani","year":"2015","unstructured":"Gianfrani, C. et al. Extensive in vitro gastrointestinal digestion markedly reduces the immune-toxicity of Triticum monococcum wheat: implication for celiac disease. Mol. Nutr. Food Res. 59, 1844\u20131854 (2015).","journal-title":"Mol. Nutr. Food Res."},{"key":"36845_CR33","doi-asserted-by":"crossref","unstructured":"Qaroni, J. Flat Bread Technology (ed. Qaroni, J.) 1\u2013206 (Chapman & Hall, 1996)","DOI":"10.1007\/978-1-4613-1175-1_1"},{"key":"36845_CR34","unstructured":"Pasqualone, A. Italian durum wheat breads. In: Bread consumption and health. (ed. Pedrosa Silva Clerici M. T.) 57\u201380 (Nova Publisher Inc., 2012)."},{"key":"36845_CR35","doi-asserted-by":"publisher","first-page":"e67280","DOI":"10.1371\/journal.pone.0067280","volume":"8","author":"G Laid\u00f2","year":"2013","unstructured":"Laid\u00f2, G. et al. Genetic Diversity and Population Structure of Tetraploid Wheats (Triticum turgidum L.) Estimated by SSR, DArT and Pedigree Data. Plos One 8, e67280 (2013).","journal-title":"Plos One"},{"key":"36845_CR36","doi-asserted-by":"publisher","first-page":"e0190162","DOI":"10.1371\/journal.pone.0190162","volume":"13","author":"G Mangini","year":"2018","unstructured":"Mangini, G. et al. Genetic dissection of the relationships between grain yield components by genome-wide association mapping in a collection of tetraploid wheats. PloS one 13, e0190162 (2018).","journal-title":"PloS one"},{"key":"36845_CR37","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.jcs.2015.08.006","volume":"67","author":"KA Scherf","year":"2016","unstructured":"Scherf, K. A. & Poms, R. E. Recent developments in analytical methods for tracing gluten. J. Cereal Sci. 67, 112\u2013122 (2016).","journal-title":"J. Cereal Sci."},{"key":"36845_CR38","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s12161-016-0573-8","volume":"10","author":"KA Scherf","year":"2017","unstructured":"Scherf, K. A. Gluten Analysis of Wheat Starches with Seven Commercial ELISA Test Kits-Up to Six Different Values. Food Anal. Methods 10, 234\u2013246 (2017).","journal-title":"Food Anal. Methods"},{"key":"36845_CR39","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.foodchem.2017.05.121","volume":"237","author":"B Lexhaller","year":"2017","unstructured":"Lexhaller, B., Tompos, C. & Scherf, K. A. Fundamental study on reactivities of gluten protein types from wheat, rye and barley with five sandwich ELISA test kits. Food Chem. 237, 320\u2013330 (2017).","journal-title":"Food Chem."},{"key":"36845_CR40","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1097\/00042737-200505000-00010","volume":"17","author":"E Garc\u00eda","year":"2005","unstructured":"Garc\u00eda, E. et al. Development of a general procedure for complete extraction of gliadins for heat processed and unheated foods. Eur. J. Gastroenterol. Hepatol. 17, 529\u2013539 (2005).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"36845_CR41","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/s00217-005-0100-4","volume":"222","author":"F Kahlenberg","year":"2006","unstructured":"Kahlenberg, F. et al. Monoclonal antibody R5 for detection of putatively coeliac-toxic gliadin peptides. Eur. Food Res. Technol. 222, 78\u201382 (2006).","journal-title":"Eur. Food Res. Technol."},{"key":"36845_CR42","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1073\/pnas.1007773107","volume":"107","author":"J Gil-Humanes","year":"2010","unstructured":"Gil-Humanes, J., Piston, F., Tollefsen, S., Sollid, L. M. & Barro, F. Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference. P. Natl. Acad. Sci. Usa 107, 17023\u201317028 (2010).","journal-title":"P. Natl. Acad. Sci. Usa"},{"key":"36845_CR43","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.foodchem.2017.04.092","volume":"234","author":"M Rzychon","year":"2017","unstructured":"Rzychon, M. et al. The feasibility of harmonizing gluten ELISA measurements. Food Chem. 234, 144\u2013154 (2017).","journal-title":"Food Chem."},{"key":"36845_CR44","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1002\/(SICI)1097-0231(20000530)14:10<897::AID-RCM962>3.0.CO;2-Z","volume":"14","author":"G Mamone","year":"2000","unstructured":"Mamone, G., Ferranti, P., Chianese, L., Scafuri, L. & Addeo, F. Qualitative and quantitative analysis of wheat gluten proteins by liquid chromatography and electrospray mass spectrometry. Rapid Commun. Mass Spectrom. 14, 897\u2013904 (2000).","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"36845_CR45","first-page":"275","volume":"67","author":"MG D\u2019egidio","year":"1990","unstructured":"D\u2019egidio, M. G., Mariani, B. M., Nardi, S., Novaro, P. & Cubadda, R. Chemical and technological variables and their relation-ships: a predictive value equation for pasta cooking quality. Cereal Chem 67, 275\u2013281 (1990).","journal-title":"Cereal Chem"},{"key":"36845_CR46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.tifs.2004.02.011","volume":"16","author":"H Goesaert","year":"2005","unstructured":"Goesaert, H. et al. Wheat flour constituents: how they impact bread quality, and how to impact their functionality. Trends Food Sci. Tech. 16, 12\u201330 (2005).","journal-title":"Trends Food Sci. Tech."},{"key":"36845_CR47","first-page":"866","volume":"37","author":"R Cubadda","year":"1992","unstructured":"Cubadda, R., Carcea, M. & Pasqui, L. A. Suitability of the gluten index method for assessing gluten strength in durum wheat and semolina. Cereal Food World 37, 866\u2013869 (1992).","journal-title":"Cereal Food World"},{"key":"36845_CR48","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1094\/CCHEM.1999.76.4.582","volume":"76","author":"NP Ames","year":"1999","unstructured":"Ames, N. P., Clarke, J. M., Marchylo, B. A., Dexter, J. E. & Woods, S. M. Effect of environment and genotype on durum wheat gluten strength and pasta viscoelasticity. Cereal Chem. 76, 582\u2013586 (1999).","journal-title":"Cereal Chem."},{"key":"36845_CR49","doi-asserted-by":"publisher","first-page":"118","DOI":"10.23986\/afsci.49570","volume":"24","author":"A Pasqualone","year":"2015","unstructured":"Pasqualone, A. et al. Quality characteristics of parental lines of wheat mapping populations. Agric Food Sci. 24, 118\u2013127 (2015).","journal-title":"Agric Food Sci."},{"key":"36845_CR50","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1002\/jsfa.2272","volume":"85","author":"MJ Sissons","year":"2005","unstructured":"Sissons, M. J., Ames, N. P., Hare, J. A. & Clarke, J. M. Relationship between glutenin subunit composition and gluten strength measurements in durum wheat. J. Sci. Food Agric. 85, 2445\u20132452 (2005).","journal-title":"J. Sci. Food Agric."},{"key":"36845_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.fcr.2011.04.001","volume":"123","author":"D Har Gil","year":"2011","unstructured":"Har Gil, D., Bonfil, D. J. & Svoray, T. Multiscale analysis of the factors influencing wheat quality as determined by Gluten Index. Field Crops Res. 123, 1\u20139 (2011).","journal-title":"Field Crops Res."},{"key":"36845_CR52","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s10681-007-9395-5","volume":"157","author":"FX Oury","year":"2007","unstructured":"Oury, F. X. & Godin, C. Yield and grain protein concentration in bread wheat: how to use the negative relationship between the two characters to identify favourable genotypes? Euphytica 157, 45\u201357 (2007).","journal-title":"Euphytica"},{"key":"36845_CR53","doi-asserted-by":"publisher","first-page":"599","DOI":"10.2135\/cropsci1972.0011183X001200050014x","volume":"12","author":"FH McNeal","year":"1972","unstructured":"McNeal, F. H., Berg, M. A., McGuire, C. F., Stewart, V. R. & Baldridge, D. E. Grain and plant nitrogen relationships in eight spring wheat crosses, Triticum aestivum L. Crop Sci. 12, 599\u2013602 (1972).","journal-title":"Crop Sci."},{"key":"36845_CR54","doi-asserted-by":"publisher","first-page":"437","DOI":"10.2134\/agronj1979.00021962007100030014x","volume":"71","author":"GL Terman","year":"1979","unstructured":"Terman, G. L. Yields and protein content of wheat grain as affected by cultivar, N, and environmental growth factors. Agron. J. 71, 437\u2013440 (1979).","journal-title":"Agron. J."},{"key":"36845_CR55","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/BF01051128","volume":"27","author":"RF Grant","year":"1991","unstructured":"Grant, R. F. The distribution of water and nitrogen in the soil-crop system: A simulation study with validation from a winter wheat field trial. Fert. Res. 27, 199\u2013213 (1991).","journal-title":"Fert. Res."},{"key":"36845_CR56","doi-asserted-by":"crossref","unstructured":"Bhatia C. R. & Rabson, R. Relationship of grain yield and nutritional quality. In Nutritional Quality of Cereal Grains: Genetics and Agronomic Management. (Eds Olson, R. A. & Frey, K. J.) 11\u201344 (American Society of Agronomy, 1987).","DOI":"10.2134\/agronmonogr28.c2"},{"key":"36845_CR57","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2229-9-41","volume":"9","author":"HC Van den Broeck","year":"2009","unstructured":"Van den Broeck, H. C. et al. Removing celiac disease-related gluten proteins from bread wheat while retaining technological properties: a study with Chinese Spring deletion lines. BMC Plant Biology 9, 41 (2009).","journal-title":"BMC Plant Biology"},{"key":"36845_CR58","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.eja.2006.08.009","volume":"26","author":"P De Vita","year":"2007","unstructured":"De Vita, P. et al. L. Breeding progress in morpho-physiological, agronomical and qualitative traits of durum wheat cultivars released in Italy during the 20th century. Eur J. Agron. 26, 39\u201353 (2007).","journal-title":"Eur J. Agron."},{"key":"36845_CR59","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1021\/jf305122s","volume":"61","author":"DD Kasarda","year":"2013","unstructured":"Kasarda, D. D. Can an increase in celiac disease be attributed to an increase in the gluten content of wheat as a consequence of wheat breeding? J. Agr. Food Chem. 61, 1155\u20131159 (2013).","journal-title":"J. Agr. Food Chem."},{"key":"36845_CR60","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1039\/C3FO60702J","volume":"56","author":"M Minekus","year":"2014","unstructured":"Minekus, M. et al. A standardised static in vitro digestion method suitable for food an international consensus. Food Funct. 56, 1113\u20131124 (2014).","journal-title":"Food Funct."},{"key":"36845_CR61","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1039\/C6FO01788F","volume":"8","author":"E De Angelis","year":"2017","unstructured":"De Angelis, E., Pilolli, R., Bavaro, S. L. & Monaci, L. Insight into the gastro-duodenal digestion resistance of soybean proteins and potential implications for residual immunogenicity. Food Funct 8, 1599\u20131610 (2017).","journal-title":"Food Funct"},{"key":"36845_CR62","doi-asserted-by":"publisher","first-page":"1700130","DOI":"10.1002\/mnfr.201700130","volume":"61","author":"R Korte","year":"2017","unstructured":"Korte, R., Br\u00e4cker, J. & Brockmeyer, J. Gastrointestinal digestion of hazelnut allergens on molecular level: Elucidation of degradation kinetics and resistant immunoactive peptides using mass spectrometry. Mol Nutr Food Res 61, 1700130 (2017).","journal-title":"Mol Nutr Food Res"},{"key":"36845_CR63","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.chroma.2014.06.092","volume":"1358","author":"L Monaci","year":"2014","unstructured":"Monaci, L., Pilolli, R., De Angelis, E., Godula, M. & Visconti, A. J. Chromatogr, A 1358, 136\u2013144 (2014).","journal-title":"J. Chromatogr, A"},{"key":"36845_CR64","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jprot.2017.03.026","volume":"163","author":"S Bromilow","year":"2017","unstructured":"Bromilow, S. et al. A curated gluten protein sequence database to support development of proteomics methods for determination of gluten in gluten-free foods. J. Proteom. 163, 67\u201375 (2017).","journal-title":"J. Proteom."},{"key":"36845_CR65","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nri3294","volume":"12","author":"JF Mohan","year":"2012","unstructured":"Mohan, J. F. & Unanue, E. R. Unconventional recognition of peptides by T cells and the implications for autoimmunity. Nat. Rev. Immunol. 12, 721\u2013728 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"36845_CR66","unstructured":"Food Allergy Research & Resource Program (FARRP), University of Nebraska, CELIAC Database, version 2, http:\/\/www.allergenonline.org\/celiachome.shtml (2018)."},{"key":"36845_CR67","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1002\/mnfr.201500769","volume":"60","author":"RE Goodman","year":"2016","unstructured":"Goodman, R. E. et al. AllergenOnline: A peer-reviewed, curated allergen database to assess novel food proteins for potential cross-reactivity. Mol. Nutr. Food Res. 60, 1183\u20131198 (2016).","journal-title":"Mol. Nutr. Food Res."},{"key":"36845_CR68","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s00251-012-0599-z","volume":"64","author":"LM Sollid","year":"2012","unstructured":"Sollid, L. M., Qiao, S., Anderson, R. P., Gianfrani, C. & Koning, F. Nomenclature and listing of celiac disease relevant gluten T-cell-epitopes restricted by HLA-DQ molecules. Immunogenetics 64, 455\u2013460 (2012).","journal-title":"Immunogenetics"},{"key":"36845_CR69","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.foodres.2017.04.025","volume":"110","author":"A Jouanin","year":"2017","unstructured":"Jouanin, A. et al. Food processing and breeding strategies for coeliac-safe and healthy wheat products. Food Res. Int. 110, 11\u201321 (2017).","journal-title":"Food Res. Int."},{"key":"36845_CR70","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1094\/CCHEM.1998.75.5.644","volume":"75","author":"H Wieser","year":"1998","unstructured":"Wieser, H., Antes, S. & Seilmeier, W. Quantitative Determination of Gluten Protein Types in Wheat Flour by Reversed-Phase High-Performance Liquid Chromatography. Cereal Chem. 75, 644\u2013650 (1998).","journal-title":"Cereal Chem."},{"key":"36845_CR71","doi-asserted-by":"publisher","DOI":"10.1007\/s10681-017-1887-3","volume":"213","author":"H Zhang","year":"2017","unstructured":"Zhang, H. et al. Genetic diversity and association mapping of agronomic yield traits in eighty-six synthetic hexaploid wheat. Euphytica 213, 111 (2017).","journal-title":"Euphytica"},{"key":"36845_CR72","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1007\/s00122-009-1173-4","volume":"120","author":"CL McIntyre","year":"2010","unstructured":"McIntyre, C. L. et al. Molecular detection of genomic regions associated with grain yield and yield-related components in an elite bread wheat cross evaluated under irrigated and rainfed conditions. Theor. Appl. Genet. 120, 527\u2013541 (2010).","journal-title":"Theor. Appl. Genet."},{"key":"36845_CR73","doi-asserted-by":"publisher","first-page":"e31249","DOI":"10.1371\/journal.pone.0031249","volume":"7","author":"X Wu","year":"2012","unstructured":"Wu, X., Chang, X. & Jing, R. Genetic insight into yield-associated traits of wheat grown in multiple rainfed environments. PLoS One 7, e31249 (2012).","journal-title":"PLoS One"},{"key":"36845_CR74","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s00122-007-0629-7","volume":"115","author":"H Kuchel","year":"2007","unstructured":"Kuchel, H., Williams, K. J., Langridge, P., Eagles, H. A. & Jefferies, S. P. Genetic dissection of grain yield in bread wheat: I. QTL analysis. Theor. Appl. Genet. 115, 1029\u20131041 (2007).","journal-title":"Theor. Appl. Genet."},{"key":"36845_CR75","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1007\/s00122-014-2322-y","volume":"127","author":"L Maphosa","year":"2014","unstructured":"Maphosa, L. et al. Genetic control of grain yield and grain physical characteristics in a bread wheat population grown under a range of environmental conditions. Theor. Appl. Genet. 127, 1607\u20131624 (2014).","journal-title":"Theor. Appl. Genet."},{"key":"36845_CR76","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1139\/y59-157","volume":"37","author":"BC Hummel","year":"1959","unstructured":"Hummel, B. C. A modified spectrophotometric determination of chymotrypsin, trypsin, and thrombin. Can. J. Biochem. Physiol. 37, 1393\u20131399 (1959).","journal-title":"Can. J. Biochem. Physiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36845-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36845-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36845-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T05:35:45Z","timestamp":1671255345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36845-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,7]]},"references-count":76,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["36845"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-36845-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,7]]},"assertion":[{"value":"20 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"1646"}}