Methylation_PBL_male_PSCUC
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010002277 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Longitudinal whole-genome DNA methylation profiling of PBL obtained from UC patients categorized as responders and non-responders
| EGAD00010002590 | EGA
Project description:Longitudinal whole-genome DNA methylation profiling of PBL obtained from IBD patients (CD and UC) at two different time points
| EGAD00010002402 | EGA
Project description:Background: Patients suffering from primary sclerosing cholangitis (PSC) often also have ulcerative colitis (UC). Cross-disease genetic and microbiome studies across PSC und UC patients indicated that UC in PSC is a separate disease entity from primary UC, but expression studies for PSC are lacking. In this study, we performed a molecular comparison of whole blood expression levels in PSC only, PSC patients with additional UC diagnosis (PSC/UC), and UC, using a large collection of whole blood transcriptome data. Methods: We conducted whole blood RNA-Seq experiments for 495 UC patients, 220 PSC patients (of whom 177 have also a UC diagnosis), and 320 healthy controls from Germany and Norway. Differential expression analyses, gene ontology and coexpression analyses and random forest machine learning were performed to identify genes, ontologies and transcriptional features that discriminate diagnoses. Results: The blood transcriptome in UC and PSC is dominated by neutrophil activation genes. In UC, but not in PSC (neither PSC alone nor PSC/UC), there is upregulation of genes for ribosomes, mitochondria and energy metabolism genes in conjunction with antibody transcript expression. In PSC, there is an increase in modules related to apoptosis and expression of genes of interferon-I-related ontologies. Random forest analysis could poorly discriminate PSC alone from PSC/UC (AUROC 0.56), but could discriminate PSC, UC, and controls with high accuracy (AUROC UC vs controls 0.95, PSC vs controls 0.88, UC vs PSC 0.986). The main coexpression modules are enriched in neutrophil degranulation and antibody production genes relevant for distinguishing PSC, UC, and controls. Conclusions: PSC and UC share neutrophil-related transcriptional upregulation in whole blood (e.g. S100A12). UC is characterised by upregulation of modules involved in antibody production (MZB1, IGJ) and increased metabolic activity (PDK4, ribosomal genes), while PSC differs from UC by interferon (IFIT1) and apoptosis upregulation (G0S2). Supported by machine learning results, PSC and UC are interpreted as molecularly separate entities, while PSC/UC and PSC are indistinguishable.
2024-01-22 | GSE177044 | GEO
Project description:Background: Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease with up to 80% of patients also suffering from ulcerative colitis (PSC-UC). The difficulty in the diagnosis along with the increased risk for developing cancer represent a clinical challenge. Furthermore, the precise molecular factors regulating the phenotype of this disease subtype remain unknown. Methods: We applied methyl-capture sequencing and mRNA sequencing to colonic mucosal biopsies from 3 groups of treatment-naïve children at diagnosis from the DOCHAS study - UC (n=10), PSC-UC (n=10) and healthy controls(n=10). Results: Differential gene expression between UC and PSC-UC identified disease-associated genes that were either up- or down-regulated in UC or PSC relative to controls. Specifically, expression of these genes was regulated by master transcriptional regulators (pro-caspases, IL7RA) and transcription factors (AR, p53, JUND, CEBPA). Importantly, gene expression comparison between UC vs PSC-UC revealed 4 up- and 4 down-regulated genes in PSC-UC patients. Notably, RAB31 and TENM3 identified as upregulated in the PSC-UC patients, are also significantly up-regulated in gastrointestinal (GI) cancers. Differential methylation analysis between controls biopsies vs PSC-UC and UC demonstrated >1000 differentially methylated regions (DMRs) with a large proportion of these DMRs enriched in enhancer regions. Conclusion: Our study, for the first time, identifies distinct gene expression and DNA methylation alterations that differentiate UC from PSC-UC at diagnosis in treatment-naïve paediatric patients, some of which are associated with GI cancers. These findings suggest the potential utility of these molecular markers as predictive biomarkers for PSC development in UC or for assessing dysplasia risk in PSC-UC. Further validation in larger patient cohorts is warranted.
2026-01-31 | GSE283289 | GEO
Project description:Bisulfite-seq data sets were generated for peripheral blood lymphocyte (PBL) and hair follicle (HF) DNA from each of two healthy males. Examination of genome-wide CpG methylation two tissues (hair follicle and peripheral blood lymphocyte) from 2 healthy male individuals.
2014-01-06 | E-GEOD-44806 | biostudies-arrayexpress
Project description:Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.
The peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry to characterize the immune cell compositions.
Genome wide methylation analysis revealed no differentially methylated positions between PSC-UC and UC patients. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While mass cytometry analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.
| EGAS00001005832 | EGA
Project description:Comparative colonic mucosal transcriptomics of 10 patients with PSC-IBD, 10 UC and 10 Healthy controls
2019-09-01 | E-MTAB-7915 | biostudies-arrayexpress
Project description:Mucosal pinch biopsies from ascending, transverse, descending colon and rectum were obtained from ulcerative colitis (UC) and primary sclerosing cholangitis concomitant with colitis (PSC-UC) patients during routine endoscopies and subjected to 5' single-cell RNA sequencing
2026-06-17 | E-MTAB-14955 | biostudies-arrayexpress
Project description:Mucosal pinch biopsies from ascending, transverse, descending colon and rectum were obtained from ulcerative colitis (UC) and primary sclerosing cholangitis concomitant with colitis (PSC-UC) patients during routine endoscopies and subjected to 5' single-cell RNA sequencing with V(D)J TCR analysis
2026-06-17 | E-MTAB-14899 | biostudies-arrayexpress
Project description:Mucosal pinch biopsies from ascending, transverse, descending colon and rectum were obtained from ulcerative colitis (UC) and primary sclerosing cholangitis concomitant with colitis (PSC-UC) patients during routine endoscopies and subjected to 5' single-cell RNA sequencing with V(D)J BCR analysis
2026-06-17 | E-MTAB-14901 | biostudies-arrayexpress