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