The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. Since the results of these 2-year bioassays are not known until quite late during development of new chemical entities, and since the short-term test battery to test for genotoxicity, a characteristic of genotoxic carcinogens, is hampered by low specificity, the identification of early biomarkers for carcinogenicity would be a big step forward. Using gene expression profiles from the livers of rats treated up to 14 days with genotoxic and non-genotoxic carcinogens we previously identified characteristic gene expression profiles for these two groups of carcinogens. We have now added expression profiles from further hepatocarcinogens and from non-carcinogens the latter serving as control profiles. We used these profiles to extract biomarkers discriminating genotoxic from non-genotoxic carcinogens and to calculate classifiers based on the support vector machine (SVM) algorithm. These classifiers then predicted a set of independent validation compound profiles with up to 88% accuracy, depending on the marker gene set. We would like to present this study as proof of the concept that a classification of carcinogens based on short-term studies may be feasible.
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sex, Specimen part
View SamplesIn this study we performed microarray-based molecular profiling of liver samples from Wistar rats exposed to genotoxic carcinogens (GC), nongenotoxic carcinogens (NGC) or non-hepatocarcinogens (NC) for up to 14 days. In contrast to previous toxicogenomics studies aimed at the inference of molecular signatures for assessing the potential and mode of compound carcinogenicity, we considered multi-level omics data. Besides evaluating the predictive power of signatures observed on individual biological levels, such as mRNA, miRNA and protein expression, we also introduced novel feature representations which capture putative molecular interactions or pathway alterations by integrating expression profiles across platforms interrogating different biological levels.
Cross-platform toxicogenomics for the prediction of non-genotoxic hepatocarcinogenesis in rat.
Sex, Specimen part
View SamplesWe report the application of RNA-seq analysis for high-throughput profiling of murine lungs infected with Aspergillus fumigatus. We compared the lung transcription of wildtype murine lungs and lungs from mice deficient in metabolic cytokine adiponectin. Overall design: Examination of 2 different mice strain and comparison of lung transcripts in response to Aspergillus fumigatus infection.
The Metabolic Cytokine Adiponectin Inhibits Inflammatory Lung Pathology in Invasive Aspergillosis.
Specimen part, Cell line, Subject
View SamplesDupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD.
Genome-wide analysis using exon arrays demonstrates an important role for expression of extra-cellular matrix, fibrotic control and tissue remodelling genes in Dupuytren's disease.
Specimen part, Disease, Disease stage
View SamplesThe double-stranded RNA binding protein Staufen2 (Stau2) is asymmetrically localized and segregated during asymmetric cell divisions in the developing mouse cortex and promotes intermediate progenitor cell fate.
Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression.
Specimen part
View SamplesThe causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan. Overall design: RNAsequencing expression profiles of livers and triceps surae hindlimb muscle from 25 week-old Ins1-/-;Ins2+/- and Ins1-/-;Ins2+/+ littermate control mice on one of two different diets (Diet A and B)
Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.
Sex, Age, Specimen part, Cell line, Subject
View SamplesWe did the RNA-seq analysis to examine the global impact of Nicotinamide (NAM) on hiPSC-derived RPE transcriptome in order to better understand the mechanism of action of NAM. NAM inhibited the expression of Age related Macular degeneration (AMD) associated protein transcripts in hiPSC-derived RPE. Overall design: Seven hiPSC-RPE lines (4 AMD donors and 3 Control donors) that had been cultured with 10mM NAM or vehicle for three weeks were used for RNA extraction and RNA-seq analysis. We treated 4 AMD hiPSC-RPE and 3 Control hiPSC-RPE lines with 10mM NAM or vehicle.
Nicotinamide Ameliorates Disease Phenotypes in a Human iPSC Model of Age-Related Macular Degeneration.
Sex, Age, Specimen part, Disease, Treatment, Subject
View SamplesMLL1 WT or KO MEF with and without HSP90 inhibitor treatment
Identification of mixed lineage leukemia 1(MLL1) protein as a coactivator of heat shock factor 1(HSF1) protein in response to heat shock protein 90 (HSP90) inhibition.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ha-ras and β-catenin oncoproteins orchestrate metabolic programs in mouse liver tumors.
Sex, Specimen part
View Samples