Methylation_PBL_male_PSCUC
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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: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: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:Cholangiocarcinoma (CCA) represents a heterogeneous group of biliary cancers with poor prognosis. Although the aetiology is generally unknown, factors like Primary Sclerosing Cholangitis (PSC) predispose to its development. Simultaneously, around 80% of patients with PSC have concomitant Ulcerative Colitis (UC). As there are no specific and sensitive biomarkers for the non-invasive diagnosis of CCA, we aimed to analyse the RNA content of serum and urine extracellular vesicles (EVs) to find accurate biomarkers of CCA that could be reflecting tumor behaviour. The transcriptomic analysis of these EVs showed a differential profile of RNAs in patients with CCA compared to healthy individuals or patients with other diseases (PSC and UC), presenting some RNAs high diagnostic values to distinguish patients with CCA. Moreover, the differential abundance of several RNAs in serum and/or urine EVs correlated with the deregulated expression of those transcripts in CCA tissue compared to surrounding liver (TCGA and Copenhagen cohorts), in tumor (EGI1, TFK1) and normal cholangiocyte (NHC) cell lines as well as in EVs secreted by those cell lines; pinpointing the potential involvement of those RNAs not only as liquid biopsy biomarkers but also as potential mediators of CCA pathogenesis.
2020-05-18 | GSE144521 | GEO
Project description:Background & Aims: Cholangiocarcinomas (CCAs), heterogeneous biliary tumors with dismal prognosis, lack accurate early-diagnostic methods, especially important for individuals at high-risk (i.e., primary sclerosing cholangitis (PSC)). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). Methods: EVs from patients with isolated PSC (n=45), concomitant PSC-CCA (n=42), PSC who developed CCA during follow-up (PSC to CCA; n=25), CCAs from non-PSC etiology (n=56), hepatocellular carcinoma (n=34) and healthy individuals (n=55) were characterized by mass-spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or CCAs regardless etiology (pan-CCAs) were defined, and their expression was evaluated in human organs/tissues and within CCA tumors at single-cell level. Prognostic EV-biomarkers for CCA were investigated. Results: High-throughput proteomics identified candidate diagnostic biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, as well as and for differential diagnosis of intrahepatic CCA and HCC, that were cross-validated by ELISA using total serum. Machine learning logit modelling disclosed CRP/FRIL/Fibrinogen algorithm with diagnostic value for early-stage PSC-CCA vs isolated PSC (AUC=0.944; OR=82.0), overpowering CA19-9 (AUC=0.735; OR=9.3). An algorithm combining CRP/VWF/PIGR/ /Fibrinogen allowed the diagnosis of early-stage non-PSC CCAs compared to healthy individuals (AUC=0.999; OR=1115). Noteworthy, levels of Fibrinogen/CRP/PIGR/FRIL showed predictive capacity for CCA development in patients with PSC before clinical evidences of malignancy. Multi-organ transcriptomic analysis revealed that serum EV-biomarkers were mostly expressed in hepatobiliary tissues, and scRNA-seq and immunofluorescence analysis of CCA tumors showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EVprognostic biomarkers independent to clinical features, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively or positively to patients’ survival, respectively. Conclusions: Serum EVs contain protein biomarkers for the prediction, early diagnosis and prognosis estimation of CCA, representing a novel tumor cell-derived liquid biopsy for personalized medicine.
2023-07-20 | PXD036943 | Pride
Project description:Background & Aims: Cholangiocarcinomas (CCAs), heterogeneous biliary tumors with dismal prognosis, lack accurate early-diagnostic methods, especially important for individuals at high-risk (i.e., primary sclerosing cholangitis (PSC)). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). Methods: EVs from patients with isolated PSC (n=45), concomitant PSC-CCA (n=42), PSC who developed CCA during follow-up (PSC to CCA; n=25), CCAs from non-PSC etiology (n=56), hepatocellular carcinoma (n=34) and healthy individuals (n=55) were characterized by mass-spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or CCAs regardless etiology (pan-CCAs) were defined, and their expression was evaluated in human organs/tissues and within CCA tumors at single-cell level. Prognostic EV-biomarkers for CCA were investigated. Results: High-throughput proteomics identified candidate diagnostic biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, as well as and for differential diagnosis of intrahepatic CCA and HCC, that were cross-validated by ELISA using total serum. Machine learning logit modelling disclosed CRP/FRIL/Fibrinogen algorithm with diagnostic value for early-stage PSC-CCA vs isolated PSC (AUC=0.944; OR=82.0), overpowering CA19-9 (AUC=0.735; OR=9.3). An algorithm combining CRP/VWF/PIGR/ /Fibrinogen allowed the diagnosis of early-stage non-PSC CCAs compared to healthy individuals (AUC=0.999; OR=1115). Noteworthy, levels of Fibrinogen/CRP/PIGR/FRIL showed predictive capacity for CCA development in patients with PSC before clinical evidences of malignancy. Multi-organ transcriptomic analysis revealed that serum EV-biomarkers were mostly expressed in hepatobiliary tissues, and scRNA-seq and immunofluorescence analysis of CCA tumors showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EVprognostic biomarkers independent to clinical features, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively or positively to patients’ survival, respectively. Conclusions: Serum EVs contain protein biomarkers for the prediction, early diagnosis and prognosis estimation of CCA, representing a novel tumor cell-derived liquid biopsy for personalized medicine.
2023-07-20 | PXD037007 | Pride
Project description:Intervention1: NIL: NIL
Control Intervention1: NIL: NIL
Primary outcome(s): 1). Comparative difference in gut microbial signatures in healthy individuals, colorectal (CRC) and ulcerative colitis (UC) patients using BugSpeaks microbiome analytical platform
2). Comparative difference in stool metabolites in healthy individuals, CRC and UC patients
Timepoint: Screening Visit (Up to day 3) Baseline Visit- Day 0
| 2721938 | ecrin-mdr-crc
Project description:Interindividual variation in methylation profiling of human DNA samples were detected using two-tissue screening by MSAM. 0.5ug of DNA was serially digested with SmaI and XmaI followed by an adaptor ligation and adaptor mediated PCR amplification HF (hair follicle) and PBL (Peripheral Blood Leukocyte) DNA samples for 8 different individuals, two-color experiment, interindividual paired comparison (same sex and age)
2010-12-01 | E-GEOD-19823 | biostudies-arrayexpress