{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:40:07Z","timestamp":1791362407328,"version":"4.3.1"},"reference-count":68,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"Deutsches Zentrum f\u00fcr Lungenforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Humans are subjected to various environmental stressors (bacteria, viruses, pollution) throughout life. As such, an inherent relationship exists between the effect of these exposures with age. The impact of these environmental stressors can manifest through DNA methylation (DNAm). However, whether these epigenetic effects selectively target genes, pathways, and biological regulatory mechanisms remains unclear. Due to the frequency of human rhinovirus (HRV) infections throughout life (particularly in early development), we propose the use of HRV under controlled conditions can model the effect of multiple exposures to environmental stressors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated a prediction model by combining transcriptome and DNAm datasets from human epithelial cells after repeated HRV infections. We applied a novel experimental statistical design and method to systematically explore the multifaceted experimental space (number of infections, multiplicity of infections and duration). Our model included 35 samples, each characterized by the three parameters defining their infection status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Trainable genes were defined by a consistent linear directionality in DNAm and gene expression changes with successive infections. We identified 77 trainable genes which could be further explored in future studies. The identified methylation sites were tracked within a pediatric cohort to determine the relative changes in candidate\u2010trained sites with disease status and age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Repeated viral infections induce an immune training response in bronchial epithelial cells. Training\u2010sensitive DNAm sites indicate alternate divergent associations in asthma compared to healthy individuals. Our novel model presents a robust tool for identifying trainable genes, providing a foundation for future studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16388","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T13:39:44Z","timestamp":1731073184000},"page":"3385-3400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Epigenetic training of human bronchial epithelium cells by repeated rhinovirus infections"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6614-9136","authenticated-orcid":false,"given":"Marua Abu","family":"Risha","sequence":"first","affiliation":[{"name":"Division of Clinical and Molecular Allergology, PA Chronic Lung Diseases Research Center Borstel  Borstel Germany"},{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9002-6930","authenticated-orcid":false,"given":"Karosham D.","family":"Reddy","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"},{"name":"Department of Paediatric Pneumology &amp; Allergology University Clinic Schleswig\u2010Holstein (UKSH)  L\u00fcbeck Germany"},{"name":"Division of Epigenetics of Chronic Lung Diseases, Priority Area Chronic Lung Diseases Research Center Borstel \u2013 Leibniz Lung Center  Borstel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3625-3373","authenticated-orcid":false,"given":"Sai Sneha Priya","family":"Nemani","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"},{"name":"Department of Paediatric Pneumology &amp; Allergology University Clinic Schleswig\u2010Holstein (UKSH)  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-0393","authenticated-orcid":false,"given":"Constanze","family":"Jakwerth","sequence":"additional","affiliation":[{"name":"Centre of Allergy and Environment (ZAUM) Technische Universit\u00e4t and Helmholtz Centre Munich  Munich Germany"},{"name":"Comprehensive Pneumology Centre Munich (CPC\u2010M) Member of The German Centre for Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3203-8084","authenticated-orcid":false,"given":"Carsten","family":"Schmidt\u2010Weber","sequence":"additional","affiliation":[{"name":"Centre of Allergy and Environment (ZAUM) Technische Universit\u00e4t and Helmholtz Centre Munich  Munich Germany"},{"name":"Comprehensive Pneumology Centre Munich (CPC\u2010M) Member of The German Centre for Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-7057","authenticated-orcid":false,"given":"Thomas","family":"Bahmer","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"},{"name":"Department of Pneumology LungenClinic Grosshansdorf  Grosshansdorf Germany"},{"name":"University Hospital Schleswig\u2010Holstein Campus Kiel Department for Internal Medicine I  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5185-9454","authenticated-orcid":false,"given":"Gesine","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pneumology, Allergology and Neonatology Hannover Medical School  Hannover Germany"},{"name":"Biomedical Research in End stage and Obstructive Lung Disease Hannover (BREATH) Member of the German Centre of Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8893-4515","authenticated-orcid":false,"given":"Erika","family":"von Mutius","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Centre Munich (CPC\u2010M) Member of The German Centre for Lung Research (DZL)  Munich Germany"},{"name":"Institute for Asthma and Allergy Prevention, Helmholtz Centre Munich German Research Centre for Environmental Health  Neuherberg Germany"},{"name":"Department of Pulmonary and Allergy, Dr von Hauner Children's Hospital, University Children's Hospital Ludwig Maximilian's University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7020-1401","authenticated-orcid":false,"given":"Klaus F.","family":"Rabe","sequence":"additional","affiliation":[{"name":"Centre of Allergy and Environment (ZAUM) Technische Universit\u00e4t and Helmholtz Centre Munich  Munich Germany"},{"name":"Comprehensive Pneumology Centre Munich (CPC\u2010M) Member of The German Centre for Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-1025","authenticated-orcid":false,"given":"Anna\u2010Maria","family":"Dittrich","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pneumology, Allergology and Neonatology Hannover Medical School  Hannover Germany"},{"name":"Biomedical Research in End stage and Obstructive Lung Disease Hannover (BREATH) Member of the German Centre of Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8084-104X","authenticated-orcid":false,"given":"Ruth","family":"Grychtol","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pneumology, Allergology and Neonatology Hannover Medical School  Hannover Germany"},{"name":"Biomedical Research in End stage and Obstructive Lung Disease Hannover (BREATH) Member of the German Centre of Lung Research (DZL)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-4218","authenticated-orcid":false,"given":"Nicole","family":"Maison","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Centre Munich (CPC\u2010M) Member of The German Centre for Lung Research (DZL)  Munich Germany"},{"name":"Institute for Asthma and Allergy Prevention, Helmholtz Centre Munich German Research Centre for Environmental Health  Neuherberg Germany"},{"name":"Department of Pulmonary and Allergy, Dr von Hauner Children's Hospital, University Children's Hospital Ludwig Maximilian's University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1652-8873","authenticated-orcid":false,"given":"Bianca","family":"Schaub","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Centre Munich (CPC\u2010M) Member of The German Centre for Lung Research (DZL)  Munich Germany"},{"name":"Department of Pulmonary and Allergy, Dr von Hauner Children's Hospital, University Children's Hospital Ludwig Maximilian's University  Munich Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ), Dr von Hauner Children's Hospital LMU Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-5492","authenticated-orcid":false,"given":"Matthias V.","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Paediatric Respiratory Medicine Inselspital, University Children's Hospital of Bern, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4307-4232","authenticated-orcid":false,"given":"Folke","family":"Brinkmann","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"},{"name":"Department of Paediatric Pneumology &amp; Allergology University Clinic Schleswig\u2010Holstein (UKSH)  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3678-7995","authenticated-orcid":false,"given":"Silke","family":"Meiners","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"},{"name":"Immunology and Cell Biology, PA Chronic Lung Diseases Research Center Borstel  Borstel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5602-3672","authenticated-orcid":false,"given":"Uta","family":"Jappe","sequence":"additional","affiliation":[{"name":"Division of Clinical and Molecular Allergology, PA Chronic Lung Diseases Research Center Borstel  Borstel Germany"},{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"},{"name":"Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5342-979X","authenticated-orcid":false,"given":"Markus","family":"Weckmann","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL) Airway Research Center North (ARCN)  Borstel Germany"},{"name":"Department of Paediatric Pneumology &amp; Allergology University Clinic Schleswig\u2010Holstein (UKSH)  L\u00fcbeck Germany"},{"name":"Division of Epigenetics of Chronic Lung Diseases, Priority Area Chronic Lung Diseases Research Center Borstel \u2013 Leibniz Lung Center  Borstel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ALLIANCE Study Group as part of the German Centre for Lung Research (DZL)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0263-z"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-015-0089-9"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01595-x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.745332"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00002"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2021"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.06.014"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000357283"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0285-6"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.07.001"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0205275"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00802-2020"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.02290-09"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.04.010"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-022-05516-5"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2012.03.008"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00207-2018"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/171.5.1329"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/315513"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.731846"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2193"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201504-0749OC"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2364-0_1"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200279"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35088-6"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.0c00385"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.12.21"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0705-6"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts034"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz031"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp101"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt019"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-8-6"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts163"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-015-0568-2"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1025"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bav006"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz840"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1072"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.691227"},{"key":"e_1_2_12_53_1","doi-asserted-by":"crossref","unstructured":"F\u00e4hnrichA ReddyKD OttF et\u00a0al.scRNA\u2010Seq Reveals Persistent Aberrant Differentiation of Nasal Epithelium Driven by TNF\u03b1 and TGF\u03b2 in Post\u2010COVID Syndrome.bioRxiv.2024. doi:10.1101\/2024.01.10.57480","DOI":"10.1101\/2024.01.10.574801"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.90151"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-017-0414-7"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2021.0193"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101013"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2021.10.004"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1080\/02770903.2021.1914649"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.37833"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1139\/y09-054"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.01.024"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00672"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0089-8"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9967-2_2"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15837"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0652-2"},{"key":"e_1_2_12_68_1","doi-asserted-by":"crossref","unstructured":"ChenY ChenL LunATL BaldoniPL SmythGK.edgeR 4.0: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets.bioRxiv.2024. doi:10.1101\/2024.01.21.576131","DOI":"10.1101\/2024.01.21.576131"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.16388","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T07:25:22Z","timestamp":1735025122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.16388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":68,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/all.16388"],"URL":"https:\/\/doi.org\/10.1111\/all.16388","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]},"assertion":[{"value":"2024-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}