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GSE70779
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Chronic hepatitis C virus (HCV) infection is now routinely treated with interferon (IFN)-free regimens composed of directly acting antiviral (DAA) agents. Changes in hepatic and peripheral innate and adaptive immune function during DAA therapy associate with achieving a sustained virologic response (SVR). The present study explored the impact of cirrhosis on host endogenous interferon pathways during DAA therapy. mRNA and micro-RNA (miRNA) expression profiling was performed on paired pre- and end-of-treatment (EOT) liver biopsies from subjects treated with a 2 DAA regimen (sofosbuvir/ledipasvir [SOF/LDV]) for 12 weeks (n=4, 3 with cirrhosis) or a 3 DAA regimen (SOF/LDV with GS-9669 or GS-9451) for 6 weeks (n=6, 0 with cirrhosis). Nine of ten subjects achieved SVR, with one relapse in the GS-9669 treatment arm (ISHAK fibrosis 4). Hepatic interferon-stimulated gene expression was down-regulated in the liver of all subjects, with no observable impact of cirrhosis or duration of treatment. Hepatic down-regulation of all type-III IFNs was observed (IFNL1, IFNL2, IFNL3, IFNL4-G), while IFNA2 expression, undetectable in all subjects pre-treatment, was detected in 3 of 9 subjects at EOT (all 3 achieved SVR). Only the subject who relapsed had detectable IFNL4-G expression in EOT liver. No change in IFNB1, IFNG, or IFNA5 expression was observed, and expression of other type-I IFNs (IFNA1, IFNA4, IFNA5, IFNA6, IFNA8, IFNA16, IFNA17) was not detected pre- or post-treatment. While expression of multiple miRNAs changed in liver tissue over the course of treatment, most miRNAs previously associated with HCV replication, innate interferon signaling, and hepatic fibrosis did not change significantly. Conclusions: Changes in the host IFN-response during DAA therapy associate with favorable treatment outcome regardless of composition and duration of therapy or extent of hepatic fibrosis.
Publication Title
Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Hepatitis C virus (HCV) chronically infects 170 million people worldwide and is a leading cause of liver-related mortality due to hepatocellular carcinoma and cirrhosis1. Standard-of-care treatment is shifting from interferon-alpha (IFN)-based to IFN-free directly acting antiviral (DAA) regimens, which demonstrate improved efficacy and tolerability in clinical trials2,3. Virologic relapse after completion of DAA therapy is a common cause of treatment failure, although mechanisms are unclear2,3. We conducted a clinical trial using the DAA sofosbuvir with ribavirin (SOF/RBV)4, and report here detailed mRNA expression analysis of pre- and end-of-treatment (EOT) liver biopsies and blood samples. On-treatment viral clearance was accompanied by rapid down-regulation of interferon-stimulated genes (ISGs) in liver and blood. Analysis of paired liver biopsies from patients who achieved a sustained virologic response (SVR) revealed that viral clearance was accompanied by decreased expression of ISGs, IFNG, and IFNLs, but increased expression of IFNA2. Patients who achieved SVR had higher expression of a hepatic type-I interferon gene signature in unpaired EOT liver biopsies than patients who later relapsed. Together, these results support a model whereby restoration of type-I intrahepatic interferon signaling at the EOT is associated with sustained hepatic HCV suppression and prevention of relapse upon withdrawal of SOF/RBV.
Publication Title
Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Mice were immunized with PCC (pigeon cytochrome c).
Publication Title
Lymphoid reservoirs of antigen-specific memory T helper cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
PP2A regulates inflammatory cytokine/chemokine gene expression by dephosphorylating protein kinases at multiple signaling pathways from stimulated cells. In this dataset, Affymetrix mouse Gene ST 2.1 Array was used to assay total RNA extracted from LPS-treated PP2AC knockout BMDM (PP2ACfl/fl;lyM-Cre) and the control BMDM (PP2ACfl/fl)
Publication Title
Myeloid-Specific Gene Deletion of Protein Phosphatase 2A Magnifies MyD88- and TRIF-Dependent Inflammation following Endotoxin Challenge.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We present a novel method of using commercial oligonucleotide expression microarrays for aCGH, enabling DNA copy number measurements and expression profiles to be combined using the same platform. This method yields aCGH data from genomic DNA without complexity reduction at a median resolution of approximately 17,500 base pairs. Due to the well-defined nature of oligonucleotide probes, DNA amplification and deletion can be defined at the level of individual genes and can easily be combined with gene expression data.
Publication Title
Gene-resolution analysis of DNA copy number variation using oligonucleotide expression microarrays.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We analyzed transcriptional changes in 4 prostate cancer cell lines following treatment with the BET inhibitor I-BET762 using Affymetrix Human Genome U133 Plus 2.0 Arrays.
Publication Title
Inhibition of BET bromodomain proteins as a therapeutic approach in prostate cancer.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 43 Downloadable Samples
NextSeq 500
Description
We report the RNA-Seq data of microglia from CK-p25 mice visual cortex Overall design: Summary of mice and treatments included in this series: CK-p25 mice - in which the expression of the Cdk5 activator p25 is driven by the excitatory neuron-specific CaMKIIa promoter in an inducible manner (CaMKIIa promoter- tTA x TetO- p25+GFP) (Cruz et al., 2003). Following withdrawal of doxycycline from the diet, CK-p25 exhibit progressive neuronal and synaptic loss with cognitive impairment, which is severe by 6 weeks of p25 induction (Cruz et al., 2003). Tau P301S mice, which express high levels of humanized mutant microtubule-associated protein tau and have tau aggregates that are associated with frontotemporal dementia as early as 5 months of age (Yoshiyama et al., 2007). 8 months old P301S mice, at which age they have synaptic and neuronal loss and cognitive deficits. CK = wild type control mice; CK-p25 + No Stim = CK-p25 mice that did not under go any stimulation; CK-p25 +GENUS = Ck-p25 mice that was stimulated with 40 Hz visual stimulation WT = wild type control mice; P301S + No Stim = P301S mice that did not under go any stimulation; P301S +GENUS = P301S mice that was stimulated with 40 Hz visual stimulation
Publication Title
Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild to moderate disease phenotypes and recover within a few weeks.
Publication Title
Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional changes were analyzed in two colorectal cancer, two pancreatic cancer, and one small cell lung cancer cell line following treatment with the BET inhibitor GSK525762 and/or the MEK inhibitor trametinib using Affymetrix Human Genome U133 Plus 2.0 Arrays.
Publication Title
MEK inhibitors overcome resistance to BET inhibition across a number of solid and hematologic cancers.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 105 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation.
Publication Title
A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts.
Sample Metadata Fields
No sample metadata fields
View Samples