Genome-Wide Methylation Profiling in 229 Patients With Crohn’s Disease Requiring Intestinal Resection: Epigenetic Analysis of the Trial of Prevention of Post-operative Crohn’s Disease (TOPPIC)

Ventham, NT; Kennedy, Nicholas A; Kalla, Rahul; Adams, Alexander T.; Noble, Alison; Mowat, Craig; Dunlop, Malcolm; Satsangi, Jack; Cahill, A; Smith, M. G.; Ahmad, Tariq; Subramanian, Sreedhar; Travis, Simon; Morris, John; Hamlin, John; Dhar, Anjan; Nwokolo, Chuka U.; Edwards, Cathryn; Creed, Tom; Bloom, Stuart; Yousif, Mohamed Omar; Thomas, Linzi; Campbell, Simon; Lewis, Stephen J.; Sebastian, Shaji; Sen, Sandip; Lal, Simon; Hawkey, Chris J.; Murray, Charles; Cummings, Fraser; Goh, Jason; Lindsay, James O.; Arebi, Naila; Potts, Lindsay; McKinley, Aileen; Thomson, John; Todd, John; Collie, Mhairi; Mowat, Ashley G; Gaya, Daniel R.; Winter, Jack; Naismith, Graham; Ennis, Holly; Keerie, Catriona; Lewis, Steff; Prescott, R. J.; Lauc, Gordan; Campbell, Harry; McGovern, Dermot; Annese, Vito; Zoldosˇ, Vlatka; Permberton, Iain K.; Wuhrer, Manfred; Kolarich, Daniel; Fernandes, Daryl L.; Theorodorou, Evropi; Spencer, V; Gardner, Richard A.; Doran, Ray; Shubhakar, Archana; Boyapati, Ray; Rudan, Igor; Lionetti, Paolo; ic´, Irena Trbojevic´ Akmac; tic´, Jasminka Kris; kovic´, Frano Vuc; Sˇtambuk, Jerko; Novokmet, Mislav; Baković, Marija; Gornik, Olga; Andriulli, Angelo; Cantoro, Laura; Sturniolo, G.C.; Fiorino, Gionata; Manetti, Natalia; Latiano, Anna; Kohn, Anna; D’Incà, R.; Danese, Silvio; Arnott, Ian; Noble, Colin; Lees, Charlie W; Shand, Alan G.; Ho, Gwo‐Tzer; Murphy, Lee; Gibson, Jude; Evenden, Louise; Wrobel, Nicola; Gilchrist, T. L.; Fawkes, Angie; Kammeijer, Guinevere S. M.; Clerc, Florent; Haan, Noortje de; Vojta, Aleksandar; Samarzˇija, Ivana; Markulin, Dora; Klasić, Marija; Dobrinić, Paula; Aulchenko, Yurii S.; Heuve, Tim van den; Jonkers, Daisy; Pierik, Marieke

doi:10.1016/j.jcmgh.2023.06.001

Cited by 3 publications

(2 citation statements)

References 69 publications

(130 reference statements)

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“…A study by Kalla et al performed multi-omic integration of the methylome, genome and transcriptome measured in the peripheral blood of UC and CD patients and identified multiple differentially methylated positions in IBD with an association with treatment escalation or need for surgery [79]. The latter group of investigators recently reported a differential and variable methylation in CD patients developing clinical recurrence after surgery [80]. The study of epigenetics in IBD is now attracting more and more attention, but it also must be considered in the context of interactions with the genome and the exposome [81].…”

Section: Epigenomicsmentioning

confidence: 99%

Omics and Multi-Omics in IBD: No Integration, No Breakthroughs

Fiocchi

2023

IJMS

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The recent advent of sophisticated technologies like sequencing and mass spectroscopy platforms combined with artificial intelligence-powered analytic tools has initiated a new era of “big data” research in various complex diseases of still-undetermined cause and mechanisms. The investigation of these diseases was, until recently, limited to traditional in vitro and in vivo biological experimentation, but a clear switch to in silico methodologies is now under way. This review tries to provide a comprehensive assessment of state-of-the-art knowledge on omes, omics and multi-omics in inflammatory bowel disease (IBD). The notion and importance of omes, omics and multi-omics in both health and complex diseases like IBD is introduced, followed by a discussion of the various omics believed to be relevant to IBD pathogenesis, and how multi-omics “big data” can generate new insights translatable into useful clinical tools in IBD such as biomarker identification, prediction of remission and relapse, response to therapy, and precision medicine. The pitfalls and limitations of current IBD multi-omics studies are critically analyzed, revealing that, regardless of the types of omes being analyzed, the majority of current reports are still based on simple associations of descriptive retrospective data from cross-sectional patient cohorts rather than more powerful longitudinally collected prospective datasets. Given this limitation, some suggestions are provided on how IBD multi-omics data may be optimized for greater clinical and therapeutic benefit. The review concludes by forecasting the upcoming incorporation of multi-omics analyses in the routine management of IBD.

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Section: Epigenomicsmentioning

confidence: 99%

Omics and Multi-Omics in IBD: No Integration, No Breakthroughs

Fiocchi

2023

IJMS

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“…These DMRs were validated with transcriptomic data and were associated with genes related to fibrosis. In patients who underwent colonic resection, five DMRs were associated with disease recurrence, including a locus associated with RPS6KA2 [ 95 ]. In another report, chromatin access and gene expression profiles were clustered into two classes that may also be used to classify CD patients [ 23 ].…”

Section: Epigenomicsmentioning

confidence: 99%

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

Kamal,

Parkash,

Beattie

et al. 2023

JCM

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Crohn’s disease (CD) is a type of inflammatory bowel disease. The number of IBD cases worldwide was estimated to be 4.9 million in 2019. CD exhibits heterogeneity in clinical presentation, anatomical involvement, disease behaviour, clinical course and response to treatment. The classical description of CD involves transmural inflammation with skip lesions anywhere along the entire gastrointestinal tract. The complexity and heterogeneity of Crohn’s disease is not currently reflected in the conventional classification system. Though the knowledge of Crohn’s pathophysiology remains far from understood, the established complex interplay of the omics—genomics, transcriptomics, proteomics, epigenomics, metagenomics, metabolomics, lipidomics and immunophenomics—provides numerous targets for potential molecular markers of disease. Advancing technology has enabled identification of small molecules within these omics, which can be extrapolated to differentiate types of Crohn’s disease. The multi-omic future of Crohn’s disease is promising, with potential for advancements in understanding of its pathogenesis and implementation of personalised medicine.

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