Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease

Background and aims: Irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease (CeD) present with similar gastrointestinal (GI) symptoms. DNA methylation-based biomarkers have not been investigated as diagnostic biomarkers to classify these disorders. We aimed to study DNA...

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Autores: Mahurkar-Joshi, Swapna, Thompson, Mike, Villarruel, Elizza, Lewis, James D., Lin, Lisa D., Farid, Mary, Nayeb-Hashemi, Hamed, Storage, Tina, Weiss, Guy A., Limketkai, Berkeley N., Sauk, Jenny S., Mayer, Emeran A., Chang, Lin
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/69524
Acceso en línea:http://hdl.handle.net/10230/69524
http://dx.doi.org/10.1111/nmo.14980
Access Level:acceso abierto
Palabra clave:Celiac disease
DNA methylation‐based biomarkers
Inflammatory bowel disease
Irritable bowel syndrome
Machine learning
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spelling Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac diseaseMahurkar-Joshi, SwapnaThompson, MikeVillarruel, ElizzaLewis, James D.Lin, Lisa D.Farid, MaryNayeb-Hashemi, HamedStorage, TinaWeiss, Guy A.Limketkai, Berkeley N.Sauk, Jenny S.Mayer, Emeran A.Chang, LinCeliac diseaseDNA methylation‐based biomarkersInflammatory bowel diseaseIrritable bowel syndromeMachine learningBackground and aims: Irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease (CeD) present with similar gastrointestinal (GI) symptoms. DNA methylation-based biomarkers have not been investigated as diagnostic biomarkers to classify these disorders. We aimed to study DNA methylation profiles of IBS, IBD, CeD, and healthy controls (HC), develop machine learning-based classifiers, and identify associated gene ontology (GO) terms. Methods: Genome-wide DNA methylation of peripheral blood mononuclear cells from 315 patients with IBS, IBD, CeD, and HC was measured using Illumina's 450K or EPIC arrays. A methylation dataset on 304 IBD and HC samples was used for external validation. Differential methylation was measured using general linear models. Classifiers were developed using penalized generalized linear models using double cross-validation controlling for confounders. Functional enrichment was assessed using GO. Results: Three hundred and fifteen participants (148 IBS, 47 IBD, 34 CeD, and 86 HC) had DNA methylation data. IBS-IBD and IBD-CeD showed the highest number of differentially methylated CpG sites followed by IBD-HC, CeD-HC, and IBS-HC. IBS-associated genes were enriched in cell adhesion and neuronal pathways, while IBD- and CeD-associated markers were enriched in inflammation and MHC class II pathways, respectively (p < 0.05). Classification performances assessed using area under the receiver operating characteristic curves (AUC) for IBS-IBD, IBS-CeD, and IBD-CeD were 0.80 (95% CI = 0.7-0.87, p = 6.75E-10), 0.78 (95% CI = 0.68-0.86, p = 4.57E-10), and 0.73 (95% CI = 0.62-0.83, p = 0.03), respectively. The performance of IBD-HC was successfully validated using external data (AUC = 0.74 [95% CI = 68-0.80, p < 0.001]). Conclusions: Blood-based DNA methylation biomarkers can potentially distinguish chronic GI disorders that present with similar symptoms. GO suggested functional significance of the classifiers in disease-specific pathology.Wiley202520252024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/69524http://dx.doi.org/10.1111/nmo.14980reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNeurogastroenterol Motil. 2024 Dec 13:e14980© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/695242026-05-29T05:05:01Z
dc.title.none.fl_str_mv Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
title Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
spellingShingle Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
Mahurkar-Joshi, Swapna
Celiac disease
DNA methylation‐based biomarkers
Inflammatory bowel disease
Irritable bowel syndrome
Machine learning
title_short Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
title_full Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
title_fullStr Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
title_full_unstemmed Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
title_sort Genome-wide DNA methylation identifies potential disease-specific biomarkers and pathophysiologic mechanisms in irritable bowel syndrome, inflammatory bowel disease, and celiac disease
dc.creator.none.fl_str_mv Mahurkar-Joshi, Swapna
Thompson, Mike
Villarruel, Elizza
Lewis, James D.
Lin, Lisa D.
Farid, Mary
Nayeb-Hashemi, Hamed
Storage, Tina
Weiss, Guy A.
Limketkai, Berkeley N.
Sauk, Jenny S.
Mayer, Emeran A.
Chang, Lin
author Mahurkar-Joshi, Swapna
author_facet Mahurkar-Joshi, Swapna
Thompson, Mike
Villarruel, Elizza
Lewis, James D.
Lin, Lisa D.
Farid, Mary
Nayeb-Hashemi, Hamed
Storage, Tina
Weiss, Guy A.
Limketkai, Berkeley N.
Sauk, Jenny S.
Mayer, Emeran A.
Chang, Lin
author_role author
author2 Thompson, Mike
Villarruel, Elizza
Lewis, James D.
Lin, Lisa D.
Farid, Mary
Nayeb-Hashemi, Hamed
Storage, Tina
Weiss, Guy A.
Limketkai, Berkeley N.
Sauk, Jenny S.
Mayer, Emeran A.
Chang, Lin
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Celiac disease
DNA methylation‐based biomarkers
Inflammatory bowel disease
Irritable bowel syndrome
Machine learning
topic Celiac disease
DNA methylation‐based biomarkers
Inflammatory bowel disease
Irritable bowel syndrome
Machine learning
description Background and aims: Irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease (CeD) present with similar gastrointestinal (GI) symptoms. DNA methylation-based biomarkers have not been investigated as diagnostic biomarkers to classify these disorders. We aimed to study DNA methylation profiles of IBS, IBD, CeD, and healthy controls (HC), develop machine learning-based classifiers, and identify associated gene ontology (GO) terms. Methods: Genome-wide DNA methylation of peripheral blood mononuclear cells from 315 patients with IBS, IBD, CeD, and HC was measured using Illumina's 450K or EPIC arrays. A methylation dataset on 304 IBD and HC samples was used for external validation. Differential methylation was measured using general linear models. Classifiers were developed using penalized generalized linear models using double cross-validation controlling for confounders. Functional enrichment was assessed using GO. Results: Three hundred and fifteen participants (148 IBS, 47 IBD, 34 CeD, and 86 HC) had DNA methylation data. IBS-IBD and IBD-CeD showed the highest number of differentially methylated CpG sites followed by IBD-HC, CeD-HC, and IBS-HC. IBS-associated genes were enriched in cell adhesion and neuronal pathways, while IBD- and CeD-associated markers were enriched in inflammation and MHC class II pathways, respectively (p < 0.05). Classification performances assessed using area under the receiver operating characteristic curves (AUC) for IBS-IBD, IBS-CeD, and IBD-CeD were 0.80 (95% CI = 0.7-0.87, p = 6.75E-10), 0.78 (95% CI = 0.68-0.86, p = 4.57E-10), and 0.73 (95% CI = 0.62-0.83, p = 0.03), respectively. The performance of IBD-HC was successfully validated using external data (AUC = 0.74 [95% CI = 68-0.80, p < 0.001]). Conclusions: Blood-based DNA methylation biomarkers can potentially distinguish chronic GI disorders that present with similar symptoms. GO suggested functional significance of the classifiers in disease-specific pathology.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/69524
http://dx.doi.org/10.1111/nmo.14980
url http://hdl.handle.net/10230/69524
http://dx.doi.org/10.1111/nmo.14980
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Neurogastroenterol Motil. 2024 Dec 13:e14980
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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