Transcription profiling by array to identify Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Almudena Espin Perez
PROVIDER: E-MTAB-7273 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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
Project description:Epigenetic profiling of birth-weight discordant twins using Illumina's 450K Human DNA methylation BeadChip Comparing DNA methylation difference in birth-weight discordant twin pairs
2014-12-15 | E-GEOD-61496 | biostudies-arrayexpress
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:In this study, we used Illumina Infinium HumanMethylation450 Beadchips to compare DNA methylation profiles in blood from 10 pairs of MZ twins and 8 individuals recruited at 0, 3, 6, and 9 months. MZ Group (Group A) contained 10 pairs of MZ twins ranging from 23 to 74 years old, including 8 female and 12 male subjects.Longitudinal study group (Group B) included a pair of MZ (male) twins and 6 unrelated individuals (3 male, 3 female), aged from 24 to 39. Except subject H, all participants in Longitudinal study group (Group B) were recalled every 3 months for 9 months (0, 3, 6, and 9 m). Subject H was studied only at 0, 6, and 9 months. Bisulphite converted DNA from the 60 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2013-10-30 | E-GEOD-51388 | biostudies-arrayexpress
Project description:Imprinted genes are critical for normal human growth and neurodevelopment. We developed a strategy to identify new DNA differentially methylated regions (DMRs), a hallmark of imprinted genes. Using genome-wide methylation profiling, candidate DMRs were selected by identifying CpGs with putative allelic differential methylation in normal biparental tissues. In parallel, we looked for parent of origin-specific DNA methylation patterns in paternally derived human androgenetic complete hydatidiform mole (AnCHM), and maternally derived mature cystic ovarian teratoma (MCT). Using this approach, we found known DMRs associated with imprinted genomic regions as well as new DMRs for known imprinted genes, NAP1L5 and ZNF597. Most importantly, novel candidate imprinted genes were identified. The paternally methylated DMR for one candidate, AXL, a receptor tyrosine kinase, was validated by methylation analyses in humans. Further validation in mouse embryos showed that Axl was expressed preferentially from the maternal allele in a DNA methylation–dependent manner. We have analyzed 3 androgenetic complete hydatidiform mole (AnCHM), 16 white blood cell (WBC), 1 mature cystic ovarian teratoma (MCT), 5 placenta, and 1 lymphoblastoid cell line paternal UPD4 sample
2011-01-26 | E-GEOD-22091 | 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:Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from mothers enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/L). Changes in iAs-associated DNA 5-methyl cytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and were compared to corresponding expression levels and birth outcomes. In the context of arsenic exposure, a total of 2,705 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyzes identified DNA methylation changes that were most predictive of gene expression levels. Specifically, CpG methylation within CpG islands positioned within the first exon and 200bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of seven of these genes were associated with differences in birth outcomes including gestational age, placental weight and head circumference. These data highlight the complex interplay between DNA methylation and functional changes in gene expression and health outcomes and underscore the need for functional analyzes coupled to epigenetic assessments. 48 DNA methylation profiles were obtained but only 38 samples corresponding to samples also analyzed for gene expression (see Rager 2014) were further normalized and used in the publication from the Biomarkers of Arsenic (BEAR) cohort were analyzed for DNA methylation profiles.
2014-11-03 | E-GEOD-62924 | 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:INTRO: The ongoing challenge of accurately diagnosing infection in the ICU motivates a search for novel molecular diagnostics. In the current study, we tested the hypothesis that the informational content of circulating leukocytes differs, thereby allowing one to rank leukocyte populations on their potential to contribute to RNA diagnostics for pneumonia. METHODS: Sixteen patients (10 male, 6 female) at risk for VAP were entered into our IRB-approved study that collects blood and clinical data every 48 hours for up to 21 days. Four of the sixteen patients developed VAP as diagnosed and treated by the attending ICU physician. Previously reported blood protocols were used to isolate buffy coat, enriched neutrophil, and enriched monocyte populations by using negative selection. Cellular purity was assessed by FACS for one of the 4 VAP patients. Genome-wide expression analysis was performed on RMA-normalized signal from Affymetrix U133 2.0 Plus GeneChips. EDGE software (FDR=0.10) was used to determine changes in mRNA abundance over time for each cell population. RESULTS: During the 5-day window in which each of the four patients (all males) developed VAP, significant changes in gene expression were observed (Table 2), but the information content (number of genes altered) varied across leukocyte populations. These differences were not due to signal variance (coefficient of variation, CV) or differences in the number of samples available for analysis. Moreover, only 0.6% of the monocyte gene list overlaps with the neutrophil list, arguing that neutrophil contamination of monocyte populations is insufficient to explain the 40-fold difference in gene number. CONCLUSIONS: Enriched monocyte populations from circulating blood provide far more genes for study of the host response to VAP than the other 2 cell populations studied. This information should be considered when designing blood gene expression profiling experiments in patients at risk for sepsis. Keywords: time course Four patients over several timepoints measured three different cell types for VAP signal
2010-09-08 | E-GEOD-12838 | biostudies-arrayexpress
Project description:Platelets are central to the pathophysiology of myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome at the time of MI and identify potential mechanisms. Platelets from patients experiencing ST-elevation myocardial infarction (STEMI) before and 3 days after treatment (n= 30), and a matched cohort of patients with severe stable coronary artery disease (CAD) prior to and 3 days after coronary artery bypass grafting (CABG, n=25) underwent quantitative proteomic analysis. Elevations of the alarmins S100A8 and S100A9 were detected at the time of STEMI compared with stable CAD (S100A8, FC = 2.00, FDR = 0.05; S100A9, FC = 2.28, FDR = 0.005). During STEMI, S100A8 mRNA and protein levels were correlated in platelets (R = 0.46, p = 0.012). To determine if protein synthesis occurs, activated platelets were incubated with 13C-labelled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was detected, consistent with the notion that protein synthesis in platelets is not a major contributor to the platelet proteome. Platelet abundance of S100A8 and A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were co-incubated under quiescent and TRAP-6 activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Leukocyte-to-platelet protein transfer, rather than protein synthesis, may occur in a thromboinflammatory environment such as STEMI, representing a potential new contributor in the innate immune pathogenesis of STEMI.
2023-11-15 | PXD024159 | Pride