4 research outputs found
Integrative Transcriptomic and Metabonomic Molecular Profiling of Colonic Mucosal Biopsies Indicates a Unique Molecular Phenotype for Ulcerative Colitis
Ulcerative
colitis is the most prevailing entity of several disorders
under the umbrella term inflammatory bowel disease, with potentially
serious symptoms and devastating consequences for affected patients.
The exact molecular etiology of ulcerative colitis is not yet revealed.
In this study, we characterized the molecular phenotype of ulcerative
colitis through transcriptomic and metabonomic profiling of colonic
mucosal biopsies from patients and controls. We have characterized
the extent to which metabonomic and transcriptomic molecular phenotypes
are associated with ulcerative colitis versus controls and other disease-related
phenotypes such as steroid dependency and age at diagnosis, to determine
if there is evidence of enrichment of differential expression in candidate
genes from genome-wide association studies and if there are particular
pathways influenced by disease-associated genes. Both transcriptomic
and metabonomic data have previously been shown to predict the clinical
course of ulcerative colitis and related clinical phenotypes, indicating
that molecular phenotypes reveal molecular changes associated with
the disease. Our analyses indicate that variables of both transcriptomics
and metabonomics are associated with disease case and control status,
that a large proportion of transcripts are associated with at least
one metabolite in mucosal colonic biopsies, and that multiple pathways
are connected to disease-related metabolites and transcripts
Box plot of RT-PCR results.
<p>Real time RT-PCR quantification of genes differentially expressed in inflamed CD smokers and non-smokers. Transcript copy numbers for ring finger protein 138 (RFP138), phosphoglucomutase 2-like 1 (PGM2L1), metallothionein 2A (MT2A), STEAP family member 3 (STEAP3), and potassium inwardly-rectifying channel, subfamily J, member 2 (KCNJ2) were measured in RNA extracted from all inflamed CD biopsy samples. The copy numbers of ribosomal protein L10 were used for normalization between samples. The box border represents the interquartile range, and the horizontal line in the box is the median. *, significant difference between smokers and non-smokers.</p
Differential expressed genes on DNA micro-arrays in CD inflamed smokers vs. CD inflamed non-smokers.
<p>The significance level for the Wilcoxon's rank sum was set at 2×10<sup>−4</sup>.</p><p>The Q value is the minimum <i>false discovery rate</i> set at 0.15.</p><p>Fold Change: up-regulated (+), down-regulated (−) in the smokers.</p