title: Integrative transcriptomic and metabonomic molecular profiling of colonic mucosal biopsies indicates a unique molecular phenotype for ulcerative colitis.
abstract: 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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17177 Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.forename: Jacob Tveiten
authors.initials: JT
authors.lastname: Bjerrum
authors.forename: Jørgen
authors.initials: J
authors.lastname: Olsen
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D003718:Denmark; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D059467:Transcriptome / Q000502:physiology*
keywords: Integrative analysis; metabonomics; molecular phenotype; transcriptomics; ulcerative colitis