Similar Datasets
Project description:<p><strong>Background</strong></p><p>This study aimed to obtain a holistic view of remission in pediatric Crohn’s Disease (CD) by integrating six omics datasets from three anatomical compartments.</p><p><br></p><p><strong>Methods</strong></p><p>Patients with fecal calprotectin below 250 mg/kg were considered in remission (n = 27), and those above 250 mg/kg as having active disease (n = 31). Proteome and microbiomes (fungi and bacteria) were analyzed in feces. Metabolomes were analyzed in feces, urine, and plasma. Datasets were integrated into a multi-omics model.</p><p><br></p><p><strong>Results</strong></p><p>The use of individual datasets shows multiple differences between remission and active disease. Integration yielded a good model (AUC of 0.8) for predicting remission. The most important features in this model are fecal bacteria (40%), fecal metabolites (22%), fecal proteins (16%), plasma metabolites (12%), fecal fungi (6%), and urine metabolites (4%). The interactome reveals Ruminococcaceae and Faecalibacterium as key players, with a correlation between antifungal urine hydroxyphenyllactic acid and fecal fungi. Pathway analysis shows an association of purine metabolism with remission, independent of thiopurine use. Changes in purine metabolism are confirmed in a pediatric CD public dataset.</p><p><br></p><p><strong>Conclusion</strong></p><p>The pathways and correlations identified as playing a role in remission may remain undetectable if individual omics datasets or single anatomical compartments are used, highlighting the need for a holistic approach that integrates multiple datasets from multiple anatomical compartments.</p>
2025-07-09 | MTBLS9877 | MetaboLights
Project description:Treatment of severely refractory Crohn’s disease (CD) patients remains a clinical challenge. Recent studies show the efficacy of autologous hematopoietic stem cell transplant (HSCT) in these severely compromised patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. We studied a group of CD patients receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanism driving efficacy, we studied changes in the immune cell composition in tissue induced by HSCT.
2019-01-23 | GSE115390 | GEO
Project description:This dataset includes RNA-seq data from ileal and colonic biopsies at time of diagnosis for treatment-naive, uncomplicated Crohn's disease (CD) patients and matched controls. This is includes 56 CD patients each for ileal and colonic tissue and for controls, 46 colonic samples and 45 ileal samples. Clinical characteristics such as development of complications, disease remission, or progression to surgery were recorded with a mean follow-up of 6 years.
2024-02-07 | GSE221161 | GEO
Project description:Objective: A subset of Crohns disease (CD) patients experiences long-term remission after infliximab withdrawal. Biomarkers are needed to identify those patients.Design: New biomarkers of relapse were searched in the baseline serum of CD patients stopping infliximab when they were under combined therapy (antimetabolite and infliximab) and stable clinical remission (STORI cohort, n=102). From shotgun proteomics experiment (discovery step), biomarker candidates were identified and further targeted by selected reaction monitoring (verification step). The dataset was stratified to search for markers of short- (<6 months) or long-term relapse (>6 months). The risk of relapse and the predicting capacity associated with biomarker candidates were evaluated using univariate Cox model and log-rank statistic, respectively. To test their complementary predicting capacity, biomarker candidates were systematically combined in pairs. Results: Distinct biomarker candidates were associated with the risk (hazard ratio: HR) of short- (15 proteins, 2.9<HR<16.1, p<0.05) and long-term (17 proteins, 2<HR<4.4, p<0.05) relapse, they reflect different pathophysiological processes. In stratified and non-stratified datasets, novel marker combinations exhibited a high predicting capacity as shown by their higher Z-scores (FDR<0.001) than CRP and faecal calprotectin (current references in predicting relapse). Conclusion: We identified for the first time circulating biomarker candidates associated with the risk of long-term relapse in CD patients stopping infliximab. We also highlight a sequence of pathophysiological processes leading to relapse, this could help to better understand the disease progression. Our findings may pave the way for a better non-invasive evaluation of the risk of relapse when contemplating anti-TNFα withdrawal in CD patients.
2020-10-19 | PXD019008 | Pride
Project description:Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission. We performed a whole-genome transcriptional analysis of peripheral whole blood (PAXgene tubes) from patients with endoscopically active and inactive UC and CD, as well as non-inflammatory controls.
2017-09-11 | GSE94648 | GEO
Project description:Creeping fat, also known as mesenteric fat, which is connected to the inflamed segments of the intestine and is a hallmark of Crohn's disease (CD), appears to be correlated with disease activity. Adipose-stem cells isolated from the creeping fat of CD subjects were found to be dysfunctional (exhibiting a high inflammatory profile, high invasive and phagocytic capacities, and worse immunosuppressive properties), and this dysfunction persisted in hASCs taken from CD subjects who were in remission of the disease. We hypothesized that the abnormal behavior of adipose stem cells is caused by the accumulation of epigenetic modifications due to the inflammatory environment underlying active CD. DNA methylation and transcriptomics were performed in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue biopsies of active and inactive CD patients and non-IBD patients. An integrative analysis of both omics was performed to obtain the best gene candidates.
2024-09-03 | GSE217163 | GEO
Project description:Creeping fat, also known as mesenteric fat, which is connected to the inflamed segments of the intestine and is a hallmark of Crohn's disease (CD), appears to be correlated with disease activity. Adipose-stem cells isolated from the creeping fat of CD subjects were found to be dysfunctional (exhibiting a high inflammatory profile, high invasive and phagocytic capacities, and worse immunosuppressive properties), and this dysfunction persisted in hASCs taken from CD subjects who were in remission of the disease. We hypothesized that the abnormal behavior of adipose stem cells is caused by the accumulation of epigenetic modifications due to the inflammatory environment underlying active CD. DNA methylation and transcriptomics were performed in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue biopsies of active and inactive CD patients and non-IBD patients. An integrative analysis of both omics was performed to obtain the best gene candidates.
2024-09-03 | GSE217124 | GEO
Project description:We analyzed publicly available mucosal gene expression data from Crohn's disease (CD) patients pre- and post-infliximab therapy and found that a series of gene expression signature that remains abnormal even if patients achieve clinical remission. Using CMap approach to discover novel therapeutic target for untreatable mechanism of anti-TNFa mAb therapy, we have identified MEK inhibitor exhibiting negatively-correlated effects on reference signature match infliximab therapy untreatable signature. Our findings provide the rationale for testing MEK inhibitor to identify a novel mechanism of action for CD. Gene expression profile was performed to analyze the gene modulation induced by a highly selective MEK inhibitor, and to evaluate whether it normalized reference residual CD signature in vitro.
2018-02-25 | GSE108050 | GEO
Project description:The natural history of Crohn's disease (CD) and ulcerative colitis (UC) is variable. In patients with frequently-relapsing/steroid-refractory disease, sustained remission is more likely if immunomodulators are introduced earlier. However, many patients experience quiescent disease without immunomodulators, and should not be unnecessarily immunosuppressed. Previous attempts to stratify treatment from diagnosis have failed because disease course cannot be reliably predicted. We performed whole genome expression analysis of peripheral CD8 and CD4 T-cells isolated from patients with active, untreated CD or UC. Patients were prospectively managed by clinicians blinded to the microarray results. Analysis of CD8 T-cell gene-expression data revealed two distinct subgroups within each disease cohort, which did not correlate with any contemporaneous laboratory or clinical data. There was considerable overlap in the genes that were differentially expressed between the subgroups in each disease. Patients belonging to one of the subgroups (termed IBD1) experienced significantly more aggressive disease than those in the other (termed IBD2) in both diseases. This was characterised by a greater need to escalate treatment with immunomodulators or surgery in response to relapsing or chronically active disease. Furthermore, this subgroup more frequently required additional interventions due to the initial escalation failing to maintain disease remission. Similar association with disease behaviour could not be demonstrated with CD4 T-cell gene-expression analysis, nor with previously described methods of predicting outcome. Our findings demonstrate that gene-expression profiling of CD8 T-cells at diagnosis can stratify patients with CD or UC according to subsequent disease behaviour and represents a significant step towards personalised therapy.
2011-07-19 | E-MTAB-331 | biostudies-arrayexpress
Project description:Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.
2024-11-19 | GSE282122 | GEO