In silico models may identify biomarkers of celiac disease
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The use of in silico models is an effective method for identifying biomarkers of celiac disease, according to a presentation at the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition Annual Meeting.
“We have found that metabolic modeling can provide a functional link to RNA-seq data,” Isabelle Aldridge, an undergraduate research assistant at the University of Virginia’s Gastroenterology Data Science Lab in Charlottesville, Virginia, said during the presentation. “We have demonstrated the value of this in silico method in identifying disease biomarkers and druggable targets which will bring us closer to celiac disease precision medicine.”
Aldridge, Philip Fernandes, of the department of pediatrics at the University of Virginia School of Medicine, and colleagues used celiac disease data that was publicly available from Israel as well as Recon3D, which accounts for the function of 3,695 annotated human genes, 13,543 metabolic reactions and 4,138 metabolites, to identify metabolites as potential diagnostic biomarkers for celiac disease. The data used from the RNA-seq included 54 patients (mean age, 8.17 years; 52% female), of which 33 had celiac disease and 21 were controls. RIPTiDe, a flux balance analysis method, was used to identify energy-efficient pathways. Multiple points from each patient’s contextualized metabolic model were generated with a flux sampling method.
Investigators identified discriminative reactions between celiac disease and controls using a random forest model and then grouped them into biological themes.
Aldridge and colleagues found glycolysis, fatty acid metabolism, phosphatidylethanolamine, alcohol dehydrogenase and the pentose phosphate pathway were among the exhibited alternations.
“The dysregulation of glycolytic metabolism is likely pivotal in celiac disease development,” Aldridge said. “Celiac patients have an impairment in glycolysis, resulting in an increase of beta oxidation. This dysregulation explains both observed lower lactate levels and the higher glucose levels in the blood of potential celiac patients. Aerobic glycolysis may also have a signaling role to promote expression of inflammatory cytokines. Phosphatidylethanolamine is the second most common cause for lipid in the human body. Phosphatidylethanolamine is the major source of arachidonic acid, which is a second messenger role against oxidative damage.”
Aldridge said fatty acid oxidation dysregulation is “central” to celiac disease. In addition, it can lead to an imbalance of pro- vs. anti-inflammatory mediators.
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Aldridge I, et al. Abstract 453. Presented at: North American Society for Pediatric Gastroenterology, Hepatology & Nutrition Annual Meeting; Dec. 12-18, 2021 (virtual meeting).
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