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Single-cell transcriptomics and bulk T-cell receptor beta-chain sequencing of peripheral blood mononuclear cells from patients with inflammatory bowel disease II (Crohn's disease and ulcerative colitis) and healthy controls

ABSTRACT: We profiled peripheral blood mononuclear cells (PBMCs) from patients with Crohn's disease (CD), ulcerative colitis (UC), and healthy controls (HC) using single-cell RNA sequencing (BD Rhapsody Targeted Analysis, Parse Evercode WT v2) and bulk T-cell receptor beta-chain sequencing (Adaptive ImmunoSEQ hsTCRB v4). A subset of donors provided matched samples for both assays.

ORGANISM(S): Homo sapiens

PROVIDER: GSE330123 | GEO | 2026/05/24

REPOSITORIES: GEO

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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.

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Single-cell transcriptomics and bulk T-cell receptor beta-chain sequencing of peripheral blood mononuclear cells from patients with inflammatory bowel disease II (Crohn's disease and ulcerative colitis) and healthy controls

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