Characterization of terminal-ileal and colonic Crohn's disease in treatment-naive paediatric patients based on transcriptomic profile using logistic regression

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Title
Characterization of terminal-ileal and colonic Crohn's disease in treatment-naive paediatric patients based on transcriptomic profile using logistic regression
Author(s)
Ilkyu Park; Jaeeun Jung; Sugi Lee; Kunhyang Park; jea-Woon Ryu; Mi-Young SonHyun-Soo ChoDae Soo Kim
Bibliographic Citation
Journal of Translational Medicine, vol. 19, pp. 250-250
Publication Year
2021
Abstract
Background: Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disorder of the gastrointestinal tract and comprises ulcerative colitis (UC) and Crohn's disease (CD). Crohn's disease can affect any part of the gastrointestinal tract, but mainly the terminal ileum and colon. In the present study, we aimed to characterize terminal-ileal CD (ICD) and colonic CD (CCD) at the molecular level, which might enable a more optimized approach for the clinical care and scientific research of CD. Methods: We analyzed differentially expressed genes in samples from 23 treatment-naive paediatric patients with CD and 25 non-IBD controls, and compared the data with previously published RNA-Seq data using multi-statistical tests and confidence intervals. We implemented functional profiling and proposed statistical methods for feature selection using a logistic regression model to identify genes that are highly associated in ICD or CCD. We also validated our final candidate genes in independent paediatric and adult cohorts. Results: We identified 550 genes specifically expressed in patients with CD compared with those in healthy controls (p < 0.05). Among these DEGs, 240 from patients with CCD were mainly involved in mitochondrial dysfunction, whereas 310 from patients with ICD were enriched in the ileum functions such as digestion, absorption, and metabolism. To choose the most effective gene set, we selected the most powerful genes (p-value ≤ 0.05, accuracy ≥ 0.8, and AUC ≥ 0.8) using logistic regression. Consequently, 33 genes were identified as useful for discriminating CD location; the accuracy and AUC were 0.86 and 0.83, respectively. We then validated the 33 genes with data from another independent paediatric cohort (accuracy = 0.93, AUC = 0.92) and adult cohort (accuracy = 0.88, AUC = 0.72). Conclusions: In summary, we identified DEGs that are specifically expressed in CCD and ICD compared with those in healthy controls and patients with UC. Based on the feature selection analysis, 33 genes were identified as useful for discriminating CCD and ICD with high accuracy and AUC, for not only paediatric patients but also independent cohorts. We propose that our approach and the final gene set are useful for the molecular classification of patients with CD, and it could be beneficial in treatments based on disease location.
Keyword
Crohn’s diseaseColonic CDTerminal-ileal CDPaediatric patientsTranscriptomic profleLogistic regression
ISSN
1479-5876
Publisher
Springer-BMC
DOI
http://dx.doi.org/10.1186/s12967-021-02909-z
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > Core Facility Management Center > 1. Journal Articles
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
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