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      Mucosal Gene Expression in Pediatric and Adult Patients With Ulcerative Colitis Permits Modeling of Ideal Biopsy Collection Strategy for Transcriptomic Analysis

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          Abstract

          <div class="section"> <a class="named-anchor" id="s1"> <!-- named anchor --> </a> <h5 class="section-title" id="d522016e404">Background</h5> <p id="d522016e406">Transcriptional profiling has been performed on biopsies from ulcerative colitis patients. Limitations in prior studies include the variability introduced by inflammation, anatomic site of biopsy, extent of disease, and medications. We sought to more globally understand the variability of gene expression from patients with ulcerative colitis to advance our understanding of its pathogenesis and to guide clinical study design. </p> </div><div class="section"> <a class="named-anchor" id="s2"> <!-- named anchor --> </a> <h5 class="section-title" id="d522016e409">Methods</h5> <p id="d522016e411">We performed transcriptional profiling on 13 subjects, including pediatric and adult patients from 2 hospital sites. For each patient, we collected 6 biopsies from macroscopically inflamed tissue and 4 biopsies from macroscopically healthy-appearing tissue. Isolated RNA was used for microarray gene expression analysis utilizing Affymetrix Human Primeview microarrays. Ingenuity pathway analysis was used to assess over-representation of gene ontology and biological pathways. RNAseq was also performed, and differential analysis was assessed to compare affected vs unaffected samples. Finally, we modeled the minimum number of biopsies required to reliably detect gene expression across different subject numbers. </p> </div><div class="section"> <a class="named-anchor" id="s3"> <!-- named anchor --> </a> <h5 class="section-title" id="d522016e414">Results</h5> <p id="d522016e416">Transcriptional profiles co-clustered independently of the hospital collection site, patient age, sex, and colonic location, which parallels prior gene expression findings. A small set of genes not previously described was identified. Our modeling analysis reveals the number of biopsies and patients per cohort to yield reliable results in clinical studies. </p> </div><div class="section"> <a class="named-anchor" id="s4"> <!-- named anchor --> </a> <h5 class="section-title" id="d522016e419">Conclusions</h5> <p id="d522016e421">Key findings include concordance, including some expansion, of previously published gene expression studies and similarity among different age groups. We also established a reliable statistical model for biopsy collection for future clinical studies. </p> </div>

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          Author and article information

          Journal
          Inflammatory Bowel Diseases
          Oxford University Press (OUP)
          1078-0998
          1536-4844
          December 2018
          November 29 2018
          July 31 2018
          December 2018
          November 29 2018
          July 31 2018
          : 24
          : 12
          : 2565-2578
          Affiliations
          [1 ]Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, Massachusetts
          [2 ]Department of Medicine, Harvard Medical School, Boston, Massachusetts
          [3 ]Pfizer Worldwide Research and Development, Cambridge, Massachusetts
          [4 ]Division of Gastroenterology, Hepatology and Endoscopy, Brigham & Women’s Hospital, Boston, Massachusetts
          [5 ]Division of Pediatric Gastroenterology, Hepatology and Nutrition, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel
          [6 ]Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
          Article
          10.1093/ibd/izy242
          6265054
          30085215
          2d7324e1-4ced-4826-8f8b-48f69954ec49
          © 2018

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