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Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Organization of the genome in 3D nuclear-space is known to play a crucial role in regulation of gene expression. However, the chromatin architecture that impinges on the B cell-fate choice of multi-potent progenitors remains unclear. By employing in situ Hi-C, we have identified distinct sets of genomic loci that undergo a developmental switch between permissive and repressive compartments during B-cell fate commitment. Intriguingly, we show that topologically associating domains (TADs) represent co-regulated subunits of chromatin and display considerable structural alterations as a result of changes in the cis-regulatory interaction landscape. The extensive rewiring of cis-regulatory interactions is closely associated with differential gene expression programs. Further, we demonstrate the regulatory role of Ebf1 and its downstream factor, Pax5, in chromatin reorganization and transcription regulation. Together, our studies reveal that alterations in promoter and cis-regulatory interactions underlie changes in higher-order chromatin architecture, which in turn determines cell-identity and cell-type specific gene expression patterns.
Publication Title
Developmentally regulated higher-order chromatin interactions orchestrate B cell fate commitment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 191 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The process for evaluating chemical safety is inefficient, costly, and animal intensive. There is growing consensus that the current process of safety testing needs to be significantly altered to improve efficiency and reduce the number of untested chemicals. In this study, the use of short-term gene expression profiles was evaluated for predicting the increased incidence of mouse lung tumors. Animals were exposed to a total of 26 diverse chemicals with matched vehicle controls over a period of three years. Upon completion, significant batch-related effects were observed. Adjustment for batch effects significantly improved the ability to predict increased lung tumor incidence. For the best statistical model, the estimated predictive accuracy under honest five-fold cross-validation was 79.3% with a sensitivity and specificity of 71.4 and 86.3%, respectively. A learning curve analysis demonstrated that gains in model performance reached a plateau at 25 chemicals, indicating that the size of the current data set was sufficient to provide a robust classifier. The classification results showed a small subset of chemicals contributed disproportionately to the misclassification rate. For these chemicals, the misclassification was more closely associated with genotoxicity status than efficacy in the original bioassay. Statistical models were also used to predict dose-response increases in tumor incidence for methylene chloride and naphthalene. The average posterior probabilities for the top models matched the results from the bioassay for methylene chloride. For naphthalene, the average posterior probabilities for the top models over-predicted the tumor response, but the variability in predictions were significantly higher. The study provides both a set of gene expression biomarkers for predicting chemically-induced mouse lung tumors as well as a broad assessment of important experimental and analysis criteria for developing microarray-based predictors of safety-related endpoints.
Publication Title
Use of short-term transcriptional profiles to assess the long-term cancer-related safety of environmental and industrial chemicals.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 1314 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Rat Genome 230 2.0 Array (rat2302), Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The MAQC-II Project: A comprehensive study of common practices for the development and validation of microarray-based predictive models
Publication Title
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Compound
View Samples- Homo sapiens
- 549 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The multiple myeloma (MM) data set (endpoints F, G, H, and I) was contributed by the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences (UAMS, Little Rock, AR, USA). Gene expression profiling of highly purified bone marrow plasma cells was performed in newly diagnosed patients with MM. The training set consisted of 340 cases enrolled on total therapy 2 (TT2) and the validation set comprised 214 patients enrolled in total therapy 3 (TT3). Plasma cells were enriched by anti-CD138 immunomagnetic bead selection of mononuclear cell fractions of bone marrow aspirates in a central laboratory. All samples applied to the microarray contained more than 85% plasma cells as determined by 2-color flow cytometry (CD38+ and CD45-/dim) performed after selection. Dichotomized overall survival (OS) and eventfree survival (EFS) were determined based on a two-year milestone cutoff. A gene expression model of high-risk multiple myeloma was developed and validated by the data provider and later on validated in three additional independent data sets.
Publication Title
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sample Metadata Fields
Sex, Age
View Samples
GSE24363- Rattus norvegicus
- 410 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302), Affymetrix Human Genome U133A Array (hgu133a)
Description
The NIEHS data set (endpoint C) was provided by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (Research Triangle Park, NC, USA). The study objective was to use microarray gene expression data acquired from the liver of rats exposed to hepatotoxicants to build classifiers for prediction of liver necrosis. The gene expression compendium data set was collected from 418 rats exposed to one of eight compounds (1,2-dichlorobenzene, 1,4-dichlorobenzene, bromobenzene, monocrotaline, N-nitrosomorpholine, thioacetamide, galactosamine, and diquat dibromide). All eight compounds were studied using standardized procedures, i.e. a common array platform (Affymetrix Rat 230 2.0 microarray), experimental procedures and data retrieving and analysis processes.
Publication Title
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sample Metadata Fields
Sex, Specimen part, Compound
View Samples- Homo sapiens
- 267 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The human breast cancer (BR) data set (endpoints D and E) was contributed by the University of Texas M. D. Anderson Cancer Center (MDACC, Houston, TX, USA). Gene expression data from 230 stage I-III breast cancers were generated from fine needle aspiration specimens of newly diagnosed breast cancers before any therapy. The biopsy specimens were collected sequentially during a prospective pharmacogenomic marker discovery study between 2000 and 2008. These specimens represent 70-90% pure neoplastic cells with minimal stromal contamination. Patients received 6 months of preoperative (neoadjuvant) chemotherapy including paclitaxel, 5-fluorouracil, cyclophosphamide and doxorubicin followed by surgical resection of the cancer. Response to preoperative chemotherapy was categorized as a pathological complete response (pCR = no residual invasive cancer in the breast or lymph nodes) or residual invasive cancer (RD), and used as endpoint D for prediction. Endpoint E is the clinical estrogen-receptor status as established by immunohistochemistry. RNA extraction and gene expression profiling were performed in multiple batches over time using Affymetrix U133A microarrays. Genomic analysis of a subset of this sequentially accrued patient population were reported previously. For each endpoint, the first 130 cases were used as a training set and the next 100 cases were used as an independent validation set.
Publication Title
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sample Metadata Fields
Age, Specimen part, Race
View Samples GSE24061- Mus musculus
- 88 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Hamner data set (endpoint A) was provided by The Hamner Institutes for Health Sciences (Research Triangle Park, NC, USA). The study objective was to apply microarray gene expression data from the lung of female B6C3F1 mice exposed to a 13-week treatment of chemicals to predict increased lung tumor incidence in the 2-year rodent cancer bioassays of the National Toxicology Program. If successful, the results may form the basis of a more efficient and economical approach for evaluating the carcinogenic activity of chemicals. Microarray analysis was performed using Affymetrix Mouse Genome 430 2.0 arrays on three to four mice per treatment group, and a total of 70 mice were analyzed and used as the MAQC-II's training set (GEO Series GSE6116). Additional data from another set of 88 mice were collected later and provided as the MAQC-II's external validation set (this Series). The training dataset had already been deposited in GEO by its provider and its accession number is GSE6116.
Publication Title
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sample Metadata Fields
Specimen part, Compound
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studies in vitro and in mice indicate a role for Coenzyme Q10 (CoQ10) in gene expression. To determine this function in relationship to physiological readouts, a 2-week supplementation study with the reduced form of CoQ10 (ubiquinol, Q10H2, 150 mg/d) was performed in 53 healthy males. Mean CoQ10 plasma levels increased 4.8-fold after supplementation. Transcriptomic and bioinformatic approaches identified a gene-gene interaction network in CD14-positive monocytes, which functions in inflammation, cell differentiation and PPAR-signaling. These Q10H2-induced gene expression signatures were also described previously in liver tissues of SAMP1 mice. Biochemical as well as NMR-based analyses showed a reduction of LDL cholesterol plasma levels after Q10H2 supplementation. This effect was especially pronounced in atherogenic small dense LDL particles (19-21 nm, 1.045 g/l). In agreement with gene expression signatures, Q10H2 reduces the number of erythrocytes but increases the concentration of reticulocytes. In conclusion, Q10H2 induces characteristic gene expression patterns, which are translated into reduced LDL cholesterol levels and erythropoiesis in humans.
Publication Title
Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The hilum region of the mouse ovary, the transitional/junction area between OSE, mesothelium and tubal (oviductal) epithelium is identified as a previously unrecognized stem cell niche of the OSE. OSE cells with high ALDH1 activity have been predominantly detected in the hilum region by immunohistochemical staining.
Publication Title
Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.
Sample Metadata Fields
Age, Specimen part
View Samples