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SRP069801
Mus musculus
53 Downloadable Samples
Illumina HiSeq 2000
Description
A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences. Overall design: This dataset includes RNA-Seq data of mRNA that were extracted from the liver of 55 male mice. The 55 mice belong to 29 different collaborative cross strains. The number of individual mice per strains is 3 for 3 strains, 2 for 16 strains, and 1 for 8 strains. All the mice are naïve without any special treatment.
Publication Title
Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine cardiac transcription profile in cyanotic Tetralogy of Fallot patients subjected to conrolled reoxygenation cardiopulmonary bypass, we collected myocardial samples at the end of the ischemic time. The transcriptional profile of the mRNA in these samples was measured with gene array technology
Publication Title
Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine cardiac transcription profile in cyanotic Tetralogy of Fallot patients subjected to hyperoxic/standard cardiopulmonary bypass, we collected myocardial samples at the end of the ischemic time. The transcriptional profile of the mRNA in these samples was measured with gene array technology
Publication Title
Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 6 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
To determine the changes in intra-renal gene expression in a novel large animal model of post Cardiopulmonary Bypass (CPB) acute kidney injury, we collected renal medulla samples obtained 24hours post intervention.
Publication Title
Changes in renal medulla gene expression in a pre-clinical model of post cardiopulmonary bypass acute kidney injury.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Morphogenesis of the mammary gland relies on the precise developmental control of morphological elements including TEBs, ducts and lobules. In the peripubertal mammary gland, rising levels of ovarian hormones control this development through a tightly controlled genetic program where specific sets of genes are up-regulated.
Publication Title
In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Danio rerio
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
We profiled genome-wide accesssible chromatin data and RNA-seq from four species (zebrafish, stickleback, mouse, and human) to identify commonly regulated genes and regulatory metods in intestinal epithelial cells (IECs). We identify a group genes that are commonly expressed in IECs and genes that are commonly expressed along the length of the intestine in fish and mammals. Using accessible chromatin data we identified enriched transcription factor binding site motifs In IECs and sites that are commonly accessible in IECs in all species. Finally, we confirm the ability for these regions from multiple species to drive conserved expression in IECs using a zebrafish reporter assay. Overall design: Examination of expression levels and chromatin accessibility in intestinal epithelaial cells in zebrafish
Publication Title
Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Analysis of gene expression levels in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions
Publication Title
Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 33 Downloadable Samples
- IlluminaHiSeq2500
Description
There is a need for reliable prognostic markers that can guide therapeutic intervention in Crohn’s disease (CD). We examined whether different behavioral phenotypes in CD can be classified based on colonic miRNA or mRNA expression and if miRNAs have prognostic utility for CD. We perform high-throughput sequencing of small RNA and mRNA isolated from colon tissue from CD patients and non-IBD (NIBD) controls. To identify miRNA and genes associated with specific behavioral phenotypes of CD, patients were stratified according to disease behavior (non-stricturing, non-penetrating; stricturing; penetrating) and compared miRNA profiles in each class with those of the NIBD group. Using a novel statistical simulation approach applied to colonic RNA-seq data for CD patients and NIBD controls, we identify at drivers of gene expression profiles associated with CD. Overall design: Macroscopically non-inflamed colon tissue from well-characterized Crohn''s disease patients and normal controls were obtained. Small RNA-seq and RNA-seq were performed on these samples. Additionally, we investigated the effect of inflammation on miRNA expression by performing small RNA-seq on matched colon samples obtained from macroscopically inflamed regions from a subset (six) of these patients with Crohn''s Disease.
Publication Title
MicroRNAs Classify Different Disease Behavior Phenotypes of Crohn's Disease and May Have Prognostic Utility.
Sample Metadata Fields
No sample metadata fields
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