Mucosal transcriptome of rectal biopsies in treatment-naïve, pediatric ulcerative colitits patients
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ABSTRACT: Using recal mucosal biopsies, collected prior to treatment in new-onset pediatric ulcerative colitis patients, we performed RNAsequencing to generate transcriptomic profiles linked to pathogenesis, severity, and treatment response.
Project description:PROTECT is a multicenter pediatric inception cohort study of response to standardized colitis therapy. In order to more explicitly model progression to colectomy within one year of diagnosis, we performed differential expression analysis between baseline rectal RNAseq biopsies of 21 patients who progressed to colectomy, and 310 who did not. We report rectal gene expression of pediatric patients with ulcerative colitis at diagnosis and at one year follow-up.
Project description:Expression data was used to evaluate changes to the transcriptional signatures across the healthy and inflamed colon. A comparison between healthy controls and active ulcerative colitis signatures was also made. Mucosal biopsy specimens were harvested at four anatomical locations within the colon from healthy volunteers and patients with active ulcerative colitis. specimens were fixed in RNA later for 24 hours at room temperature and stored at -80C for a further 24 hours prior to RNA extraction and microarray analysis.
Project description:Expression data was used to evaluate changes to the transcriptional signatures across the healthy and inflamed colon. A comparison between healthy controls and active ulcerative colitis signatures was also made.
Project description:The etiology of the inflammatory bowel diseases, including ulcerative colitis, remains incomplete, but recent findings points to the involvement of complex host-microbial interactions. We hypothesized that an analysis of the proteins on the host-microbial interacting surface, the intestinal mucosa, could reveal novel insights into the diseases. Mucosal colonic biopsies were extracted by standard colonscopy from sigmoideum from 10 ulcerative colitis patients from non-inflammed tissue and 10 controls. The biopsies were immediately following extraction snap-frozen for protein analysis and the protein content of the biopsies was characterized by high-throughput quantative gel-free proteomics.
Project description:The gold of this study is to identify genes that differentially expressed in rectum of ulcerative colitis patients who are responisve to tofacitinib compared with the patients who are refractory to the drug. This study may help to identify preditive markers to determine tofacitinib responders prior to the treatment.
Project description:RNA was isolated from rectal biopsies from 190 pediatric patients undergoing diagnostic colonoscopy for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Single-end, 75-bp sequencing was performed, and raw reads aligned to the human genome using Gencode v 24 as reference. We included 14085 protein-coding mRNA genes in downstream analyses, where cutoffs of fold change>1.5 and FDR<0.05 were considered significant.
Project description:Ulcerative colitis (UC) is an idiopathic chronic inflammatory disorder of the colonic mucosa with rising incidence. Despite numerous known genetic risk loci environmental factors seem to be crucial in the pathogenesis of this complex disease with suboptimal treatment options. Approaches utilizing methods of systemic biology have been started to use in the analysis of mucosal biopsies in order to get a more comprehensive view of the changes related to the disorder. Our aim was to test the capability of a new mass spectrometry (MS) -based assay (PCT-SWATH mass spectrometry) to characterize host proteomes both in inflamed and non-inflamed colon tissues of an UC patient cohort.
Project description:Infliximab, an anti-TNF-alpha monoclonal antibody, is an effective treatment for ulcerative colitis (UC) with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-TNF-alpha is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in UC. Keywords: drug response