Background: Patients with early stage non-small cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial. Here, we assessed its value in an independent set of cases.
Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients.
Sex, Age
View SamplesPreeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We hypothesized that this heterogeneity is due to the existence of multiple molecular forms of PE. To address our hypothesis, we created a large (N=330) human placental microarray data set consisting of seven previously published studies (GSE30186, GSE10588, GSE24129, GSE25906, GSE43942, GSE4707, and GSE44711) and 157 highly annotated samples from a BioBank (below).
Unsupervised Placental Gene Expression Profiling Identifies Clinically Relevant Subclasses of Human Preeclampsia.
Specimen part, Disease
View SamplesChanges in endothelial phenotype induced by E. coli-derived Shiga toxins (Stx) are believed to play a critical role in the pathogenesis of hemolytic uremic syndrome. Stx inactivate host ribosomes, but also alter gene expression at concentrations that minimally affect global protein synthesis. The effect of Stx on the gene expression profile of human microvascular endothelial cells was examined using the Affymetrix HG-U133A platform. Data were processed using 13 different methods and revealed 369 unique differentially expressed genes, 318 of which were up-regulated and 51 of which were down-regulated. These studies implicated activation of the CXCR4/CXCR7/SDF-1 chemokine pathway in Stx-mediated pathogenesis.
The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice.
Sex
View SamplesPurpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT.
Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer.
Sex, Age, Specimen part
View SamplesPreeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We recently identified five clusters of placentas within a large gene expression microarray dataset (N=330, GSE75010), of which four contained a substantial number of PE samples. However, while transcriptional analysis of placentas can subtype patients, we hypothesized that the addition of epigenetic information should reveal gene regulatory mechanisms behind the distinct PE pathologies. We, therefore, subjected 48 of our samples to Infinium Human Methylation 450K arrays and investigated relationships between the gene expression and DNA methylation data.
Epigenetic regulation of placental gene expression in transcriptional subtypes of preeclampsia.
Sex, Specimen part, Disease
View SamplesJust as animal monozygotic twins can experience different environmental conditions by being reared apart, individual genetically-identical trees of the genus Populus can also be exposed to contrasting environmental conditions by being grown in different locations. As such, clonally-propagated Populus trees provide an opportunity to interrogate the impact of individual environmental history on current response to environmental stimuli. To test the hypothesis that current responses to an environmental stimulus, drought, are contingent on environmental history, the transcriptome-level drought responses of three economically important hybrid genotypes: DN34 (Populus deltoides x P. nigra); Walker (P. deltoides var. occidentalis x (P. laurifolia x P. nigra)); and, Okanese (Walker x (P. laurifolia x P. nigra)) derived from two different locations were compared. Strikingly, differences in transcript abundance patterns in response to drought were based on differences in geographic origin of clones for two of the three genotypes. This observation was most pronounced for the genotypes with the longest time since establishment and last common propagation. Differences in genome-wide DNA methylation paralleled the transcriptome level trends, where the clones with the most divergent transcriptomes and clone history had the most marked differences in the extent of total DNA methylation, suggesting an epigenetic basis for the clone-history-dependent transcriptome divergence. The data provide insights into the interplay between genotype and environment in the ecologically and economically important Populus genus, with implications for both the industrial application of Populus trees, and the evolution and persistence of these important tree species.
Clone history shapes Populus drought responses.
Specimen part, Treatment
View SamplesC3H/HeJ, BalbC/J, C57BL/6J, C57BL10/J, C57BLKS/J, C57L/J strains were tested for variability in gene expression in hippocampus, striatal, and brainstem tissues to affiliate findings with behavioural prepulse inhibition scores
Pdxdc1 modulates prepulse inhibition of acoustic startle in the mouse.
Sex, Specimen part
View SamplesAs exposure to episodic drought can impinge significantly on forest health and the establishment of productive tree plantations, there is great interest in understanding the mechanisms of drought response in trees. The ecologically dominant and economically important genus Populus, with its sequenced genome, provides an ideal opportunity to examine transcriptome level changes in trees in response to a drought stimulus. The transcriptome level drought response of two commercially important hybrid Populus clones (P. deltoides P. nigra, DN34, and P. nigra P. maximowiczii, NM6) was characterized over a diurnal period using a 4 2 2 completely randomized factorial ANOVA experimental design (four time points, two genotypes, and two treatment conditions) using Affymetrix Poplar GeneChip microarrays. Notably, the specific genes that exhibited changes in transcript abundance in response to drought differed between the genotypes and/or the time of day that they exhibited their greatest differences. This study emphasizes the fact that it is not possible to draw simple, generalized conclusions about the drought response of the genus Populus on the basis of one species, nor on the basis of results collected at a single time point. The data derived from our studies provide insights into the variety of genetic mechanisms underpinning the Populus drought response, and provide candidates for future experiments aimed at understanding this response across this economically and ecologically important genus.
Genotype and time of day shape the Populus drought response.
Age, Specimen part, Treatment
View SamplesWe examined the gene expression profiles in ex vivo human CD4+ and CD8+ T cells from untreated HIV-infected individuals at different clinical stages and rates of disease progression. Profiles of pure CD4+ and CD8+ T cells subsets from HIV-infected nonprogressors who controlled viremia were indistinguishable from HIV-uninfected individuals. Similarly, no gene clusters could distinguish T cells from individuals with early from chronic progressive HIV infection, whereas differences were observed between uninfected or nonprogressors versus early or chronic progressors. In early/chronic HIV infection, three characteristic gene expression signatures were observed: (1) CD4+ and CD8+ T cells showed increased expression of interferon stimulated genes (ISGs). However, some ISGs including CXCL9, CXCL10, and CXCL11, and the IL15R in both CD4+ and CD8+ T cells and the anti-HIV ISG APOBEC3G in CD4+ T cells, were not upregulated. (2) CD4+ and CD8+ T cells showed a cluster similar to that observed in thymocytes, and (3) more genes were differentially regulated in CD8+ T cells than in CD4+ T cells, including a cluster of genes downregulated exclusively in CD8+ T cells. In conclusion, HIV infection induces a persistent T cell transcriptional profile, early in infection, characterized by a dramatic but potentially aberrant interferon response, and a profile suggesting an active thymic output.
Distinct transcriptional profiles in ex vivo CD4+ and CD8+ T cells are established early in human immunodeficiency virus type 1 infection and are characterized by a chronic interferon response as well as extensive transcriptional changes in CD8+ T cells.
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Specimen part
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