Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human colon biopsies obtained from patients with ulcerative colitis, Chrohn's disease vs. normal to identify pathogenic processes underlying these disease subtypes

ABSTRACT: Ulcerative colitis (UC) and Crohns disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies. To identify pathogenic processes underlying these disease subtypes, using single endoscopic pinch biopsies to estabolish 36 expression profiles, we elucidated gene expression patterns of active and inactive areas of UC and CD, and compared these to infectious colitis and healthy controls.To identify pathogenic processes underlying these disease subtypes, using single endoscopic pinch biopsies, we elucidated gene expression patterns of active and inactive areas of UC and CD, and compared these to infectious colitis and healthy controls. An unsupervised classification of a total of 36 samples yielded promising separation between IBD affected, unaffected, non-IBD colitis and normal controls, suggesting distinctive gene expression patterns for each sample type. The Significance Analysis of Microarays (SAM) software to select biologically significant changes in gene expression between groups. The criteria selected for SAM analysis are, a median false discovery rate (FDR) ? 0.00001%, fold change >2, and a Log2 mean expression index > 6.64.

ORGANISM(S): Homo sapiens

SUBMITTER: Shukti Chakravarti

PROVIDER: E-GEOD-6731 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis.

Wu Feng F Dassopoulos Themistocles T Cope Leslie L Maitra Anirban A Brant Steven R SR Harris Mary L ML Bayless Theodore M TM Parmigiani Giovanni G Chakravarti Shukti S

Inflammatory bowel diseases 20070701 7

<h4>Background</h4>Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD) with variable, overlapping clinical features and complex pathophysiologies.<h4>Methods</h4>To identify pathogenic processes underlying these disease subtypes, we used single endoscopic pinch biopsies to elucidate patterns of gene expression in active and inactive areas of UC and CD and compared these to infectious colitis and healthy control samples.<h4>Results</h4>Unsupervised classificatio ...[more]

PMID: 17262812

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Project description:Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn’s disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD. In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in inflamed and non-inflamed colon pinch biopsies from the IBD patients using expression microarrays platform. In this study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In case of inflamed CD and UC (iCD and iUC), we identified 438 and 745 differentially expressed lncRNAs, respectively, while in case of the non-inflamed CD and UC (niCD and niUC), we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment (p-value < 0.001, Pearson’s Chi-squared test) for 96 differentially expressed lncRNAs and 154 protein-coding genes within the IBD susceptibility loci. Furthermore, we found strong positive expression correlations for the intersecting and cis-neighboring differentially expressed IBD loci-associated lncRNA-protein-coding gene pairs. The functional annotation analysis of differentially expressed genes revealed that they are involved in immune response, pro-inflammatory cytokine activity and MHC protein complex. The lncRNA expression profiling in both inflamed and non-inflamed CD and UC, successfully stratified IBD patients from the healthy controls. Taken together, the identified lncRNA transcriptional signature along with clinically relevant parameters suggests their potential as biomarkers in IBD. A total of 96 biopsy samples (including 6 samples used as technical replicates) extracted from different colonic locations from 45 patients (CD=13, UC=20, Controls=12) were profiled using Agilent Custom 8x60K format lncRNA expression microarray. In Gencode v15 lncRNA microarray design, each lncRNA transcript is targeted by two probes covering 22,001 lncRNA transcripts corresponding to 12,963 lncRNA genes. In addition, each array contains 17,535 randomly-selected protein-coding targets, of which 15,182 (unique 12,787) correspond to protein-coding genes.

Project description:Background and Aims: The diagnosis of Inflammatory Bowel Diseases (IBD), ulcerative colitis (UC), and Crohn's disease (CD), relies on clinical and pathologic criteria. Non-invasive precision medicine tools to diagnose IBD and discriminate between UC and CD are needed to personalize management. Serum proteomics identified protein biomarkers capable of diagnosing IBD and differentiating Crohn’s disease from ulcerative colitis subtypes. Methods: We obtained serum samples from 47 IBD and non-IBD patients seen in a tertiary care pediatric gastroenterology clinic and applied SomaScan proteomics to measure 1,305 proteins to discriminate between IBD and non-IBD and UC and CD. Four proteins were further validated by immunoassays in two cohorts of 295 and 105 individuals and multi-protein predictors were developed using Support Vector Machines (SVM). Findings: The SomaScan discovery phase identified 95 serum protein biomarkers (BH p<0.01) that differentiated IBD from non-IBD and 70 proteins (p<0.01) that distinguished UC from CD. Pathway analysis linked specific inflammatory processes and vascular functions to IBD and UC versus CD. An 8-protein classifier achieved an AUC of 0.95 for identifying IBD. Significant elevation of four key predictor proteins (MMP1, MMP3, Resistin, Haptoglobin) in IBD was validated by ELISA in the expanded cohort (N=295). The 4-protein SVM predictor achieved an AUC of 0.86 and 0.90 for IBD discrimination in two independent cohorts. A separate 4-protein SVM predictor for differentiating UC from CD achieved an AUC of 0.93 in independent validation. Interpretation: Patients with pediatric-onset IBD have a unique serum protein signature associated with pro-inflammatory and vascular pathways. Additional studies are needed to determine whether these dysregulated proteins can be used in conjunction with traditional risk factors to support non-invasive biomarkers that identify IBD and discriminate between its subtypes. The diagnosis of Inflammatory Bowel Diseases (IBD), ulcerative colitis (UC), and Crohn's disease (CD), relies on clinical and pathologic criteria. Non-invasive precision medicine tools to diagnose IBD and discriminate between UC and CD are needed to personalize management. Serum proteomics identified protein biomarkers capable of diagnosing IBD and differentiating Crohn’s disease from ulcerative colitis subtypes. Methods We obtained serum samples from 47 IBD and non-IBD patients seen in a tertiary care pediatric gastroenterology clinic and applied SomaScan proteomics to measure 1,305 proteins to discriminate between IBD and non-IBD and UC and CD. Four proteins were further validated by immunoassays in two cohorts of 295 and 105 individuals and multi-protein predictors were developed using Support Vector Machines (SVM). Findings Som The SomaScan discovery phase identified 95 serum protein biomarkers (BH p<0.01) that differentiated IBD from non-IBD and 70 proteins (p<0.01) that distinguished UC from CD. Pathway analysis linked specific inflammatory processes and vascular functions to IBD and UC versus CD. An 8-protein classifier achieved an AUC of 0.95 for identifying IBD. Significant elevation of four key predictor proteins (MMP1, MMP3, Resistin, Haptoglobin) in IBD was validated by ELISA in the expanded cohort (N=295). The 4-protein SVM predictor achieved an AUC of 0.86 and 0.90 for IBD discrimination in two independent cohorts. A separate 4-protein SVM predictor for differentiating UC from CD achieved an AUC of 0.93 in independent validation. Interpretation Patients with pediatric-onset IBD have a unique serum protein signature associated with pro-inflammatory and vascular pathways. Additional studies are needed to determine whether these dysregulated proteins can be used in conjunction with traditional risk factors to support non-invasive biomarkers that identify IBD and discriminate between its subtypes.

Dataset Information

Transcription profiling of human colon biopsies obtained from patients with ulcerative colitis, Chrohn's disease vs. normal to identify pathogenic processes underlying these disease subtypes

Publications

Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis.

Similar Datasets

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