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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- Homo sapiens
- 3 Downloadable Samples
IlluminaGenomeAnalyzer
Description
Transcriptome profiling studies suggest that a large fraction of the genome is transcribed and many transcripts function independent of their protein coding potential. The relevance of noncoding RNAs (ncRNAs) in normal physiological processes and in tumorigenesis is increasingly recognized. Here, we describe consistent and significant differences in the distribution of sense and antisense transcripts between normal and neoplastic breast tissues. Many of the differentially expressed antisense transcripts likely represent long ncRNAs. A subset of genes that mainly generate antisense transcripts in normal but not cancer cells is involved in essential metabolic processes. These findings suggest fundamental differences in global RNA regulation between normal and cancer cells that might play a role in tumorigenesis. Overall design: Global strand-specific transcriptome profilings of 2 samples in cancer and 1 sample in normal from clinical breast tissue using asymmetrical strand-specific analysis of gene expression (ASSAGE).
Publication Title
Altered antisense-to-sense transcript ratios in breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum and cortex are functionally connected with increasing degrees
Publication Title
Systems-based analyses of brain regions functionally impacted in Parkinson's disease reveals underlying causal mechanisms.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
RNA-Seq has been increasingly used for the quantification and characterization of transcriptomes. The ongoing development of the technology promises the more accurate measurement of gene expression. However, its benefits over widely accepted microarray technologies have not been adequately assessed, especially in toxicogenomics studies. The goal of this study is to enhance the scientific community''s understanding of the advantages and challenges of RNA-Seq in the quantification of gene expression by comparing analysis results from RNA-Seq and microarray data on a toxicogenomics study. A typical toxicogenomics study design was used to compare the performance of an RNA-Seq approach (Illumina Genome Analyzer II) to a microarray-based approach (Affymetrix Rat Genome 230 2.0 arrays) for detecting differentially expressed genes (DEGs) in the kidneys of rats treated with aristolochic acid (AA), a carcinogenic and nephrotoxic chemical most notably used for weight loss. We studied the comparability of the RNA-Seq and microarray data in terms of absolute gene expression, gene expression patterns, differentially expressed genes, and biological interpretation. We found that RNA-Seq was more sensitive in detecting genes with low expression levels, while similar gene expression patterns were observed for both platforms. Moreover, although the overlap of the DEGs was only 40-50%, the biological interpretation was largely consistent between the RNA-Seq and microarray data. RNA-Seq maintained a consistent biological interpretation with time-tested microarray platforms while generating more sensitive results. However, there is clearly a need for future investigations to better understand the advantages and limitations of RNA-Seq in toxicogenomics studies and environmental health research. Overall design: Eight rats were randomly divided into two groups: four rats were administered with aristolochic acid (AA), and four rats were treated with the control vehicle. RNA samples were extracted from the kidney tissue of each rat and were independently assayed with both the NGS (Illumina Genome Analyzer II) and the microarray (Affymetrix Rat Genome 230 2.0) platforms. The RNA-Seq and microarray data were compared in terms of absolute gene expression, gene expression patterns, differentially expressed genes, and biological interpretation.
Publication Title
An investigation of biomarkers derived from legacy microarray data for their utility in the RNA-seq era.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
Recurrent mutations in histone modifying enzymes in multiple cancer types imply key roles in tumorigenesis. However, the functional relevance of these mutations remains unknown. Here we show that the JARID1B histone H3 lysine 4 demethylase is frequently amplified and overexpressed in luminal breast tumors and a somatic point mutation of JARID1B leads to the gain of luminal-specific gene expression programs. Downregulation of JARID1B in luminal breast cancer cells induces the expression of basal cell-specific genes and growth arrest, which is partially rescued by the inhibition of TGFBR thereby indicating a key role for TGFb signaling. Integrated genome-wide analysis of JARID1B chromatin binding, histone H3 lysine trimethyl (H3K4me3) and dimethyl (H3K4me2) patterns, and gene expression profiles in luminal and basal-like breast cancer cells suggest a key role for JARID1B in luminal cell-specific gene expression programs. A significant fraction of JARID1B binding-sites overlaps with CTCF in both luminal and basal-like breast cancer cells. CTCF also co-immunoprecipitates with JARID1B and it may influence its histone demethylase (HDM) activity as the H3K4me3/me2 ratio is lower at the CTCF-overlapping compared to JARID1B-unique sites. Additionally, a heterozygous JARID1B missense mutation (K1435R) in the HCC2157 basal-like breast cancer cell line is associated with unique JARID1B chromatin-binding and gene expression patterns implying gain of luminal features. In line with this, exogenous expression of this mutant in basal-like breast cancer cells leads to a gain of JARID1B binding at many luminal-specific genes. A PARADIGM score reflecting JARID1B activity in luminal breast cancer cells is associated with poor clinical outcome in patients with luminal breast tumors. Together, our data imply that JARID1B is a luminal lineage-driving oncogene and that its therapeutic targeting may represent a novel therapeutic strategy in treatment-resistant luminal breast tumors. Overall design: RNA-Seq in breast cancer cell-lines transfected with JARID1B/CTCF/control siRNA. 50 cycles of sequencing on Illumina platform.
Publication Title
JARID1B is a luminal lineage-driving oncogene in breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 105 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The comparative advantages of RNA-Seq and microarrays in transcriptome profiling were evaluated in the context of a comprehensive study design. Gene expression data from Illumina RNA-Seq and Affymetrix microarrays were obtained from livers of rats exposed to 27 agents that comprised of seven modes of action (MOAs); they were split into training and test sets and verified with real time PCR.
Publication Title
The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Publication Title
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative. Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype. We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients.
Publication Title
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
Sample Metadata Fields
Cell line
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GSE1847- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Hepatic gene expression analysis in mice fed control diet or diets supplemented with 1% Fraction 1 (haxane) or Fraction 2 (methanol) of Boswellia Serrata
Publication Title
Effects of Boswellia serrata in mouse models of chemically induced colitis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Decreased mitochondrial mass and function in muscle of diabetic patients is associated with low PGC-1alpha, a transcriptional coactivator of the mitochondrial gene program. To investigate whether reduced PGC-1alpha and oxidative capacity in muscle directly contributes to age-related glucose intolerance, we compared the genetic signatures and metabolic profiles of aging mice lacking muscle PGC-1alpha. Microarray analysis revealed that a significant proportion of PGC-1alpha-dependent changes in gene expression overlapped with age-associated effects, and aging muscle and muscle lacking PGC-1alpha shared gene signatures of impaired electron transport chain activity and TGFbeta signalling.
Publication Title
Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation.
Sample Metadata Fields
Specimen part
View Samples