The Implications of DNA Methylation on Food Allergy

Lee, Khui Hung; Song, Yong; O’Sullivan, Michael; Pereira, Gavin; Loh, Richard; Zhang, Guicheng

doi:10.1159/000479513

Cited by 10 publications

(10 citation statements)

References 64 publications

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“…DNA methylation is the most commonly known type of long‐term epigenetic modification, with transcriptional activity being directly affected by level of methylation . Methylation and demethylation of DNA have been implicated in food allergy through several mechanisms yet the role of vitamin D has been seldom explored . Junge et al highlighted the significance of the relationship between vitamin D levels and a gene involved in allergic inflammation, thymic stromal lymphopoietin ( TSLP ).…”

Section: Vitamin D Modulation At the Epigenetic Levelmentioning

confidence: 99%

Cellular and molecular mechanisms of vitamin D in food allergy

Poole

Song

Brown

et al. 2018

J Cellular Molecular Medi

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Food allergies are becoming increasingly prevalent, especially in young children. Epidemiological evidence from the past decade suggests a role of vitamin D in food allergy pathogenesis. Links have been made between variations in sunlight exposure, latitude, birth season and vitamin D status with food allergy risk. Despite the heightened interest in vitamin D in food allergies, it remains unclear by which exact mechanism(s) it acts. An understanding of the roles vitamin D plays within the immune system at the cellular and genetic levels, as well as the interplay between the microbiome and vitamin D, will provide insight into the importance of the vitamin in food allergies. Here, we discuss the effect of vitamin D on immune cell maturation, differentiation and function; microbiome; genetic and epigenetic regulation (eg DNA methylation); and how these processes are implicated in food allergies.

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Section: Vitamin D Modulation At the Epigenetic Levelmentioning

confidence: 99%

Cellular and molecular mechanisms of vitamin D in food allergy

Poole

Song

Brown

et al. 2018

J Cellular Molecular Medi

Self Cite

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“…Martino et al 2015 [14] provides proof of principle that genome-wide levels of DNA Methylation, an epigenetic tag, are strong diagnostic markers of clinical FA. There is a high volume of recent FA research that uses DNAm: Martino et al 2018 [15] used integrated DNAm and transcriptome profiling to conclude that the activation of naive CD4+ T cells results in poorer lymphoproliferative responses in children with FA, Sicherer and Sampson 2018 [16] suggest the use of DNAm signatures to create FA-related diagnostic tests, and Song et al 2017 [17] state that DNAm regulates genes that are critical for the development of FA.…”

Section: Introductionmentioning

confidence: 99%

Machine learning approach yields epigenetic biomarkers of food allergy: A novel 13-gene signature to diagnose clinical reactivity

Alag¹

2019

PLoS ONE

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Background Current laboratory tests are less than 50% accurate in distinguishing between people who have food allergies (FA) and those who are merely sensitized to foods, resulting in the use of expensive and potentially dangerous Oral Food Challenges. This study presents a purely-computational machine learning approach, conducted using DNA Methylation (DNAm) data, to accurately diagnose food allergies and potentially find epigenetic targets for the disease. Methods and results An unbiased feature-selection pipeline was created that narrowed down 405,000+ potential CpG biomarkers to 18. Machine-learning models that utilized subsets of this 18-feature aggregate achieved perfect classification accuracy on completely hidden test cohorts (on an 8-fold hidden dataset). Ensemble classification was also shown to be effective for this High Dimension Low Sample Size (HDLSS) DNA methylation dataset. The efficacy of these machine learning classifiers and the 18 CpGs was further validated by their high accuracy on a large number of hidden data permutations, where the samples in the training, cross-validation, and hidden sets were repeatedly randomly allocated. The 18-CpG signature mapped to 13 genes, on which biological insights were collected. Notably, many of the FA-discriminating genes found in this study were strongly associated with the immune system, and seven of the 13 genes were previously associated with FA. Conclusions Previous studies have also created highly-accurate classifiers for this dataset, using both data-driven and a priori biological insights to construct a 96-CpG signature. This research builds on previous work because it uses a completely computational approach to obtain a perfect classification accuracy while using only 18 highly discriminating CpGs (0.005% of the total available features). In machine learning, simpler models, as used in this study, are generally preferred over more complex ones (other things being equal). Lastly, the completely data-driven methodology presented in this research eliminates the need for a priori biological information and allows for generalizability to other DNAm classification problems.

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“…The important role of vitamin D in DNA methylation has been observed in Treg cells. It is well known that stable levels of Tregs depend on FOXP3 methylation; consequently, low levels of vitamin D reduce Treg population through change in methylation on FOXP3, increasing therefore the risk of FA [79]. In contrast, a negative correlation on Treg cells and vitamin D, showing that high levels of vitamin D could suppress Treg number through the methylation of FOXP3 increasing the risk of FA development has been also reported [79].…”

Section: The Role Of Vitamin D Epigenetics In Food Allergymentioning

confidence: 99%

Epigenetics in Food Allergy and Immunomodulation

et al. 2021

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Food allergy (FA) is an increasing problem worldwide and, over recent years, its prevalence is rising in developed countries. Nowadays, the immunological and cellular processes that occur in the allergic reactions are not fully understood, which hampers the development of in vitro diagnostic tools and further treatment options. Moreover, allergic diseases could be reinforced by environmental exposure and genetic modifications. Gene expression can be controlled by different epigenetic mechanisms like DNA methylation, histone modifications, and microRNAs. In addition, several environmental factors such as dietary components (vitamin D, butyrate, folic acid) are able to regulate this epigenetic mechanism. All these factors produce modifications in immune genes that could alter the development and function of immune cells, and therefore the etiology of the disease. Furthermore, these epigenetic mechanisms have also an influence on immunomodulation, which could explain sustained responsiveness or unresponsiveness during immunotherapy due to epigenetic modifications in key genes that induce tolerance in several FA. Thus, in this review we focus on the different epigenetic mechanisms that occur in FA and on the influence of several dietary components in these gene modifications.

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The Implications of DNA Methylation on Food Allergy

Cited by 10 publications

References 64 publications

Cellular and molecular mechanisms of vitamin D in food allergy

Cellular and molecular mechanisms of vitamin D in food allergy

Machine learning approach yields epigenetic biomarkers of food allergy: A novel 13-gene signature to diagnose clinical reactivity

Epigenetics in Food Allergy and Immunomodulation

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