Early-passage (<10 passages) cultures of melanoma cells from metastatic lymph node lesions and normal adult melanocytes explanted in parallel from the adjacent, non-involved skin of 5 patients were compared by cDNA arrays. Differences between normal and neoplastic counterparts were then assessed upon adjustment for individual factors.
A melanoma immune response signature including Human Leukocyte Antigen-E.
Sex, Specimen part
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 SamplesAnalysis of the transcriptional profiles of mRNA and microRNA in Rasless fibroblasts. 4-Hydroxy-tamoxifen (4-OHT) treatment triggers removal of K-Ras expression in [H-Ras-/-;N-Ras-/-;K-Raslox/lox;RERTert/ert ] mouse fibroblasts (named K-Raslox) generating Rasless MEFs which are unable to proliferate, but recover proliferative ability after ectopic expression of constitutively active downstream kinases such as BRAF and MEK1.
Reversible, interrelated mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts: functional and mechanistic implications.
Specimen part, Cell line, Treatment
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 SamplesThe 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 SamplesFull title: Prepubertal Human Spermatogonia and Mouse Gonocytes Share Conserved Gene Expression of Germline Stem Cell Regulatory Molecules
Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules.
Age
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 SamplesPurpose: RNA-Seq analysis can help identify large set of differentially expressed genes at a time. We performed RNA-Seq analysis to identify differentially expressed genes in the PBMCs of war veterans suffering from PTSD. Methods: Total RNA from PBMCs from PTSD +ve and -ve individuals were used for RNA-Seq analysis. Results: We obtained, on average, ~60 millions reads per sample. More than 70% of the reads were mapped to human genome. Functional analysis of the differentially expressed genes (362) revealed dysregulation in immune system network. Conclusions: Our present study provides further proof that immune system related genes and pathways are dysregulated in PTSD PBMCs. Overall design: RNA-Seq was performed with RNA from 5 each control and PTSD individuals. PBMCs collected within one hour of blood draw were used for RNA isolation. 1 ug of total RNA was used for library synthesis and sequenced in a HighSeq 2000 illumina instrument at Tufts University.
Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation.
Specimen part, Subject
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