期刊论文详细信息
Journal of Translational Medicine
Characterization of terminal-ileal and colonic Crohn’s disease in treatment-naïve paediatric patients based on transcriptomic profile using logistic regression
Dae-Soo Kim1  Ilkyu Park1  Sugi Lee1  Kunhyang Park2  Jaeeun Jung3  Jea-Woon Ryu4  Mi-Young Son5  Hyun-Soo Cho5 
[1] Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, Korea;Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141, Daejeon, Korea;Department of Core Facility Management Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Korea;Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, 34141, Daejeon, Korea;Department of Rare Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Korea;Department of Stem Cell Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Korea;
关键词: Crohn’s disease;    Colonic CD;    Terminal-ileal CD;    Paediatric patients;    Transcriptomic profile;    Logistic regression;   
DOI  :  10.1186/s12967-021-02909-z
来源: Springer
PDF
【 摘 要 】

BackgroundInflammatory 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.MethodsWe analyzed differentially expressed genes in samples from 23 treatment-naïve 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.ResultsWe 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).ConclusionsIn 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.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO202109174713213ZK.pdf 2285KB PDF download
  文献评价指标  
  下载次数:4次 浏览次数:4次