CIITA
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000
ORGANISM(S): Homo sapiens
SUBMITTER: Wanseon Lee
PROVIDER: E-MTAB-2424 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The epigenetic regulation of transcription factor genes is critical for T cell lineage specification. A specific methylation pattern within a conserved region of the lineage specifying transcription factor gene FOXP3, the Treg-specific demethylated region (TSDR), is restricted to regulatory T (Treg) cells and required for stable expression of FOXP3 and suppressive function. We analyzed the impact of hypomethylating agents 5-Aza-2`-deoxycytidine and Epigallocatechin-3-gallate (EGCG) on human CD4+CD25- T for generating Treg cell specific DNA methylation pattern within FOXP3-TSDR and inducing functional Treg cells. Gene expression, including lineage specifying transcription factors of the major T cell lineages and their leading cytokines, functional properties and global transcriptome changes were analyzed. 5-Aza-2`-deoxycytidine induced FOXP3-TSDR methylation and expression of Treg cell specific genes FOXP3 and LRRC32. Proliferation of 5-Aza-2´deoxycytidine treated cells was reduced, but they did not show suppressive function. Hypomethylation was not restricted to FOXP3-TSDR and expression of master transcription factors and leading cytokines of Th1 and Th17 cells were induced. EGCG induced global DNA hypomethylation to a lower degree than 5-Aza-2´deoxycitidine, but no relevant hypomethylation within FOXP3-TSDR or expression of Treg cell specific genes. Both DNMT inhibitors did not induce full functional human Treg cells. Although 5-Aza-2`-deoxycytidine treated cells phenotypically appeared to be Treg cells, they did not suppress proliferation of responder cells, which is an essential capability to be used in Treg cell transfer therapy. In this study we analyze the potency of the two hypomethylating agents 5-Aza-2`-deoxycytidine (5-Aza-dC) and Epigallocatechin-3-gallate (EGCG) for in vitro induction of functional Treg cell cells through generation of a specific methylation pattern within FOXP3-TSDR. We analyzed the expression of Treg cell specific genes and for their functional properties from CD4+CD25- T cells. 5-Aza-dC is a derivative of 5-Azacytidine. Both substances are inhibitors of DNA methyltransferases (DNMTs) and used for therapy of patients with myelodysplastic syndrome and acute myeloid leukaemia. In these patients, 5-Azacytidine has been reported to augment regulatory T cell expansion in blood. EGCG is the most abundant catechin of green tea and has been reported to have cardio protective, anti-cancer, anti-infective properties and protective effects on autoimmune diseases. EGCG has also been described as a potent inhibitor of DNMTs and to induce Foxp3 in Jurkat T cell line.
2013-12-19 | E-GEOD-53448 | biostudies-arrayexpress
Project description:T-helper 1 responses are involved in the development of many autoimmune diseases such as Multiple sclerosis (MS). MS is a relapse remitting disease that eventually progresses to a progressive neurodegenerative disease. During pregnancy the relapse rate of MS is significantly reduced with peak reduction during the third trimester followed by an increase in relapse rate post-partum. One of the highest expressed hormones during pregnancy is progesterone. Progesterone has been show to have an inhibiting effect on T-cell activation and been proposed to promote a T-regulatory like cell state. To evaluate the influence of progesterone on the chromatin and gene expressive state of T-helper type 1 cells we differentiated primary human naïve T-cell in the presence progesterone with sampling at 0.5, 1, 2, 6 and 24 hours and performed ATAC-seq and RNA-seq.
2021-09-09 | E-MTAB-10423 | biostudies-arrayexpress
Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with high intra-tumoral heterogeneity, frequently resistant to treatment and no known targeted therapy available to improve patient outcomes. It has been hypothesized that the genomic architecture of a TNBC tumour evolves over time, both before, and during therapy, leading to therapy resistance and a high propensity to relapse. Whether this is an inherent property of the tumour or acquired over time is not well characterized. Despite this important clinical implication, limited studies have been carried out to unravel temporal evolution of TNBC over time. Herein, we report an OMICS based analysis of three TNBC patients who were longitudinally sampled during their treatment at different times of relapse. We recruited three TNBC patients at the time of their first relapse who were then followed-up through the course of their treatment. We obtained retrospective samples (tumour samples) from patient tumours at diagnosis (before neo-adjuvant chemotherapy - NACT) at surgery (post NACT) and prospectively sampled them at each subsequent relapse (tumour, blood plasma, and buffy coat) as determined by RECIST criteria. Tumor and buffy coat DNA were subjected to whole exome sequencing (WES) at 200x, and SNP arrays for copy number variation (CNV) analysis. RNA from tumour samples at relapse was subjected to whole transcriptome sequencing. Pathogenic germline BRCA1 variants identified in WES were validated using Sanger sequencing. 1084 somatic mutations identified in whole exome sequencing of all tumour tissues (n=13) from three patients, were subjected to a custom amplicon ultra-deep sequencing assay at 30,000X in their germline DNA (n=3), tumour DNA (n=10), and cfDNA from plasma samples at relapse (n=8). Copy number corrected allele frequencies, tumour ploidy, tumour purity, and ultra-deep sequencing assay derived variant allele frequencies were used to infer clonal and phylogenetic architecture of each patient as it evolved under selective pressure of therapy over time. Clonality analysis incorporating allele fractions from ultra-deep sequencing identified clones comprising of mutations that are present throughout the course of therapy which we term as founding clones and stem mutations respectively. Such founding clones comprising of stem mutations in all 3 patients were present throughout the course of treatment, irrespective of change in treatment modalities. These stem clones included well characterized cancer related genes like PDGFRB & ARID2 (Patient 02), TP53, BRAF & CSF3R (Patient 04) and ESR1, APC, EZH2 & TP53 (Patient 07). Such branching evolution is seen in all three patients wherein the dominant clone (stem clone) acquires additional mutations to form sub-clones, while persisting over time. These sub-clones may be chemo and radio resistant, while also providing for organ specific metastatic potential. Allele fractions of expressed variants inferred from RNA-Seq data co-related with allele fractions from WES data indicating that all somatic.
2022-12-30 | E-MTAB-11909 | biostudies-arrayexpress
Project description:GSA from 562 out of 1841 patients with severe decompensated cirrhosis from the DECISION project. The DECISION project aims to discover more personalized combinatorial therapies for patients with decompensation of cirrhosis. This will be achieved by using readily available clinical data, prospectively collected in a homogenous manner from large clinical studies, with the corresponding standardized biobank samples that will produce omics data once they are fully analyzed. The data generated and analyzed in DECISION will directly serve as a basis for accomplishing the objectives of the project, i.e.: 1. Improving our knowledge of the pathophysiology of decompensation of cirrhosis by integrating results of high-throughput multi-omic profiling with comprehensive clinical data from fully characterized patients with available biological samples. 2. Identifying novel combinatorial therapies for patients with decompensation of cirrhosis to prevent death. 3. Developing 2 tests: One predicting the outcome of patients with decompensation of cirrhosis when treated with standard treatment (prognostic test), and the other identifying patients who will respond to the novel combinatorial therapy (test for response).
2024-12-18 | E-MTAB-12555 | biostudies-arrayexpress
Project description:GSA from 278 out of 1841 patients with severe decompensated cirrhosis from the DECISION project. The DECISION project aims to discover more personalized combinatorial therapies for patients with decompensation of cirrhosis. This will be achieved by using readily available clinical data, prospectively collected in a homogenous manner from large clinical studies, with the corresponding standardized biobank samples that will produce omics data once they are fully analyzed. The data generated and analyzed in DECISION will directly serve as a basis for accomplishing the objectives of the project, i.e.: 1. Improving our knowledge of the pathophysiology of decompensation of cirrhosis by integrating results of high-throughput multi-omic profiling with comprehensive clinical data from fully characterized patients with available biological samples. 2. Identifying novel combinatorial therapies for patients with decompensation of cirrhosis to prevent death. 3. Developing 2 tests: One predicting the outcome of patients with decompensation of cirrhosis when treated with standard treatment (prognostic test), and the other identifying patients who will respond to the novel combinatorial therapy (test for response).
2024-12-18 | E-MTAB-12554 | biostudies-arrayexpress
Project description:GSA from 387 out of 1841 patients with severe decompensated cirrhosis from the DECISION project. The DECISION project aims to discover more personalized combinatorial therapies for patients with decompensation of cirrhosis. This will be achieved by using readily available clinical data, prospectively collected in a homogenous manner from large clinical studies, with the corresponding standardized biobank samples that will produce omics data once they are fully analyzed. The data generated and analyzed in DECISION will directly serve as a basis for accomplishing the objectives of the project, i.e.: 1. Improving our knowledge of the pathophysiology of decompensation of cirrhosis by integrating results of high-throughput multi-omic profiling with comprehensive clinical data from fully characterized patients with available biological samples. 2. Identifying novel combinatorial therapies for patients with decompensation of cirrhosis to prevent death. 3. Developing 2 tests: One predicting the outcome of patients with decompensation of cirrhosis when treated with standard treatment (prognostic test), and the other identifying patients who will respond to the novel combinatorial therapy (test for response).
2024-12-18 | E-MTAB-12553 | biostudies-arrayexpress
Project description:Peripheral Blood Mononuclear Cells (PBMCs) were isolated from a buffy coat (Australian Blood Bank) using Ficoll methodology. CD4+ T cells were isolated using Dynal Beads kit. Pure CD4+ T cells were then stained using a cocktail of monoclonal antobodies (mAbs), including: anti-CD4PE, CD45RO ECD, CD62L APC-Cy7, CD25 APC, CD127 Pacific Blue. After incubation, cells were washed twice in PBS/FCS (0.2%), and sorted into five different cell subsets: CD4+CD25+CD127low CD62L+CD45RO- (naive regulatory T cells), CD4+CD25+CD127low CD62L+/- CD45RO+ (activated regulatory T cells), CD4+CD25+CD127hi CD62L+/- CD45RO+ (memory T cells), CD4+CD25-CD127low CD62L+/- CD45RO+ (effector T cells) and CD4+CD25-CD127hi CD62L+ CD45RO- (naive T cells).
2011-02-10 | E-MEXP-2578 | biostudies-arrayexpress
Project description:The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identified nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.
2022-11-21 | PXD027780 | Pride
Project description:Background: Standard Guthrie cards have been widely used to collect blood samples from neonates for newborn screening programs, and to a lesser extent, from normal controls and patients in research studies. Ease of blood collection (small quantity and less pain), transportation, and storage are the advantages of using these cards. It is believed that RNA obtained from these samples is of low quantity and degraded quality. However, we recently discovered that approximately 3,500 expressed genes can be detected from blood spot samples using in-house made, low resolution cDNA microarrays. Here, we established a new and improved methodology to acquire gene expression profiles from blood spot cards using commercially-available high resolution microarrays. We determined the optimal number of blood spot punches required for maximal RNA extraction, eliminated uses of trizol and chloroform for RNA extraction by using a modified protocol of the illustra Mini Spin Kit from GE-Whatm an, concentrated the quantity of RNA templates before amplification, improved amplification efficiency using the new Ribo-SPIA technology in WT-Ovation Pico System (WT-Pico) by NuGEN, before the samples were hybridized onto 4x44K whole human genome gene expression microarrays from Agilent. Nine dried blood spot samples were collected from a control population and stored at ~ -80 °C between 6 months to 2 years. High quality RNA was extracted from the buffy coat of the same individuals as a reference and processed using the standard Agilent microarray procedure. Commercially-available brain RNA was used as a positive control in both standard and new procedures for microarrays. Results: Three 3-mm punches produced the highest yield of total RNA using the non-trizol extraction method. Three to six nanogram per microliter of RNA can be concentrated and is sufficient to be amplified using the WT-Pico. Approximately 9,000 expressed genes can be detected after normalization and background correction of the microarray data. Conclusion: Genome-wide gene expression profile can be obtained from archived dried blood spot samples. Our new and improved methodology will add value to the perception of utilizing archival Guthrie cards eg. neonatal blood spot cards as unique biospecimens for molecular genomics and diagnostic studies of perinatal diseases such as pediatric cancers. Keywords: Gene Expression experiment Archival guthrie blood-spot cards may contain valuable data for epidemiological or other studies. Showing microarray data from guthrie blood-spot cards
2012-12-07 | E-GEOD-19919 | biostudies-arrayexpress
Project description:Contemporary analyses focused on a limited number of clinical and molecular features have been unable to accurately predict clinical outcomes in pancreatic ductal adenocarcinoma (PDAC). Here we describe a novel, conceptual approach and use it to analyze clinical, computational pathology, and molecular (DNA, RNA, protein, and lipid) analyte data from 74 patients with resectable PDAC. Multiple, independent, machine learning models were developed and tested on curated singleand multi-omic feature/analyte panels to determine their ability to predict clinical outcomes in patients. The multi-omic models predicted recurrence with an accuracy and positive predictive value (PPV) of 0.90, 0.91, and survival of 0.85, 0.87, respectively, outperforming every singleomic model. In predicting survival, we defined a parsimonious model with only 589 multi-omic analytes that had an accuracy and PPV of 0.85. Our approach enables discovery of parsimonious biomarker panels with similar predictive performance to that of larger and resource consuming panels and thereby has a significant potential to democratize precision cancer medicine worldwide.
2024-01-23 | PXD037038 | Pride