The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes.
Interlobular and intralobular mammary stroma: genotype may not reflect phenotype.
No sample metadata fields
View SamplesConsider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. As contrasted to a population averaged reference, this reference sample is individualized. Automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that compare to a person's healthy reference to enhance predictive accuracy. This study develops such an individualized predictor and illustrates the added value of including the healthy reference for design of predictive gene expression panels. The objective is to predict each subject's state of infection, e.g., neither exposed nor infected, exposed but not infected, pre-acute phase of infection, acute phase of infection, post-acute phase of infection. Using gene microarray data collected in a large-scale serially sampled respiratory virus challenge study, we quantify the diagnostic advantage of pairing a person's baseline reference with his or her target sample.
An individualized predictor of health and disease using paired reference and target samples.
Specimen part, Subject, Time
View SamplesVenous thromboembolism (VTE) is a major cause of morbidity and mortality. Pulmonary embolism is a life threatening manifestation of VTE that occurs in at least half the patients on presentation. In addition, VTE recurs in up to 30% of patients after a standard course of anticoagulation, and there is not a reliable way of predicting recurrence. We investigated whether gene expression profiles of whole blood could distinguish patients with VTE from healthy controls, single VTE from those with recurrence, and DVT alone from those with PE. 70 adults with VTE on warfarin and 63 healthy controls were studied. Patients with antiphospholipid syndrome or cancer were excluded. Blood was collected in PAXgene tubes, RNA isolated, and gene expression profiles obtained using Affymetrix arrays. We developed a 50 gene model that distinguished healthy controls from subjects with VTE with excellent receiver operating characteristics (AUC 0.94; P < 0.0001). We also discovered a separate 50 gene model that distinguished subjects with a single VTE from those with recurrent VTE with good receiver operating characteristics (AUC 0.75; P=0.008). In contrast, we were unable to distinguish subjects with DVT from those with PE using gene expression profiles. Gene expression profiles of whole blood can distinguish subjects with VTE from healthy controls and subjects with a single VTE from those with recurrence. Additional studies should be performed to validate these results and develop diagnostic tests. Gene expression profiling is likely translatable to other thrombotic disorders(e.g., patients with cancer and VTE).
Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism.
Sex, Age, Race
View SamplesThe role of the beta2 adrenergic receptor (2AR) after stroke is unclear as pharmacological manipulations of the 2AR have produced contradictory results. We previously showed that mice deficient in the 2AR (2KO) had smaller infarcts compared to wild-type mice (FVB) after middle cerebral artery occlusion (MCAO), a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell death were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischemia (Ccl9, Gem, and Prg4). In addition to networks that were similar between genotypes, one network with a central node of G protein-coupled receptor and including biological functions carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in 2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype in all conditions. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in 2KO mice. As both genes are implicated in NFB signaling, we measured p65 activity and tumor necrosis factor alpha (TNF) levels 24h after MCAO. MCAO-induced p65 activation and post-ischemic TNF production were both greater in FVB compared to 2KO mice. These results suggest that loss of 2AR signaling results in a neuroprotective phenotype in part due to decreased NFB signaling, decreased inflammation, and decreased apoptotic signaling in the brain.
Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia.
Sex, Specimen part
View SamplesEnterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. We report the first gene expression analysis of the human host response to experimental challenge with ETEC.
Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.
Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain transcriptional and epigenetic associations with autism.
Age, Specimen part, Disease, Disease stage, Subject
View SamplesAutism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.
Brain transcriptional and epigenetic associations with autism.
Age
View SamplesCalorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging. Overall design: Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.
Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures.
No sample metadata fields
View SamplesGene expression profile in circulating leukocytes identifies patients with coronary artery disease
Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.
Sex, Age, Specimen part, Race
View SamplesGenome-wide expression profiling was performed on 50 core needle biopsies from 18 breast cancer patients using Affymetrix GeneChip Human Genome Plus 2.0 Arrays.
Intratumor heterogeneity and precision of microarray-based predictors of breast cancer biology and clinical outcome.
Disease, Disease stage, Subject
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