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SRP131524
Homo sapiens
12 Downloadable Samples
Illumina HiSeq 4000
Description
Using our computational method SynGeNet to evaluate genomic and transcriptomic data characterizing four major genomic subtypes of melanoma, we selected the top ranked drug combination for BRAF-mutation melanoma for subsequent validaiton. Here we present drug-induced gene expression data from the BRAF-mutant A375 melanoma cell line in response to four treatment conditions: vehicle control (DMSO), vemurafenib alone, tretinoin (ATRA) alone and vemurafenib+tretinoin combination. Overall design: Gene expression profiles of A375 melanoma cells were generated by RNAseq (Illumina HiSeq 4000) under the following treatment conditions: vehicle control (DMSO), vemurafenib, tretinoin and vemurafenib + tretinoin combination.
Publication Title
Synergy from gene expression and network mining (SynGeNet) method predicts synergistic drug combinations for diverse melanoma genomic subtypes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
This study sought to evaluate the effects of dietary MeHg exposure on adult female yellow perch (Perca flavescens) and zebrafish (Danio rerio) reproduction by relating controlled exposures with subsequent reproductive effects. Yellow perch were used in the study for their socioeconomic and ecological importance within the Great Lakes basin, and the use of zebrafish allowed for a detailed analysis of the molecular effects of MeHg. MeHg exposures at environmentally relevant levels were done in zebrafish for a full life cycle, mimicking a realistic exposure scenario, and in adult yellow perch for twenty weeks, capturing early seasonal ovarian development. In zebrafish, several genes involved in reproductive processes were shown to be dysregulated by RNA-seq and QPCR, but no significant phenotypic or physiological changes were observed with ovarian staging, fecundity, or embryo mortality. Yellow perch did not appear to be affected by MeHg, either at a molecular level, as assessed by QPCR of eight genes in the pituitary, liver, and ovary tissue, or a physiological level, as seen with ovarian somatic index, circulating estradiol, and ovarian staging. Lack of impact in yellow perch limits the usefulness of zebrafish as a model and suggests that the reproductive sensitivity to environmentally relevant levels of MeHg differs between yellow perch and zebrafish. Overall design: 12 samples of total RNA isolated from adult zebrafish ovaries were analyzed. Each exposure group (1, 3, and 10 ppm MeHg) had three replicates, as did the vehicle control. Each sample was comprised of pooled total RNA of up to 6 individual fish.
Publication Title
Female reproductive impacts of dietary methylmercury in yellow perch (Perca flavescens) and zebrafish (Danio rerio).
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 8 Downloadable Samples
Affymetrix Zebrafish Genome Array (zebrafish)
Description
2,3,7,8-TCDD (TCDD) is a reproductive toxicant and endocrine disruptor in nearly all vertebrates, yet the mechanisms by which TCDD induces these reproductive alterations have not been fully characterized. Fish are among the most sensitive vertebrates to the toxic effects of TCDD, and even subtle physiologic changes induced by TCDD can impair reproduction. Previously, we have shown that chronic, sub-lethal exposure to TCDD decreased reproductive capacity, reduced serum estradiol and vitellogenin concentrations, and altered follicular development. Here we investigate the transcriptional changes in zebrafish ovary as they relate to observed attenuated estradiol concentrations and ovarian development. We used quantitative RT-PCR to assess TCDDs effects on the expression of several candidate genes important in the regulation of follicular development and steroidogenesis. Additionally, global changes in gene expression in the ovary caused by TCDD exposure were identified using Affymetrix Gene Chip Analysis. Our data suggest that TCDD may inhibit follicle maturation via attenuated gonadotropin responsiveness and/or depressed estradiol biosynthesis. Additionally, genes involved in glucose and lipid metabolism, regulation of transcription, and immune function were dysregulated by at least 2-fold suggesting that TCDD alters various integrated networks of signaling pathways. Approximately 89% of dysregulated transcripts contain putative AHR response elements (AHRE) within 5kb upstream of the predicted transcriptional start site suggesting ovarian toxicity is AHRE driven. Furthermore, approximately 49% of dysregulated transcripts contain putative estrogen response elements (ERE) suggesting that dysregulation of estrogen-responsive genes may also contribute to TCDD-induced attenuated follicular development. Patterns in gene expression were correlated with putative EREs and AHREs, and suggest that impacts on the regulation of transcription may play a large role in TCDDs ovarian toxicity. Taken together, these data illustrate the complexity of TCDDs ovarian toxicity.
Publication Title
Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: insights into TCDD-induced endocrine disruption and reproductive toxicity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Gallus gallus
- 24 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
In the present study, we examined the hepatic transcriptome of chickens during the peri-hatch periodor the metabolic jump from chorioallantoic (embryo) to pulmonary (hatchling) respiration. Although our major interest was comparison of differentially-expressed genes between embryos and hatchlings, we made pairwise contrasts across six developmental ages. We collected the liver from four embryos at three ages (e16, e18 and e20) and four hatchling chicks at three ages (1, 3 and 9 days) post hatching. Liver samples (N=24) were used for extraction of total RNA which was then used for hybridization to 24 Affymetrix Chicken Genome Arrays. Ingenuity Pathways Analysis was used for functional annotation and mapping of differentially expressed (FDR0.05) genes to canonical pathways and gene interaction networks. We identified 1274 hepatic genes that were differentially expressed between embryos and hatchling chicks and of these, 284 genes are involved in lipid metabolism. The three most abundant found in liver of embryos were (MOGAT1, DIO3 and PDK4), whereas THRSP, FASN and DIO2 were greatly expressed in liver of hatchlings. Two functionally-distinct clusters of hepatic genes have emerged from our time-course transcriptional scans in the peri-hatch chicken. Cluster A genes are largely lipolytic with higher expression in the embryo, while Cluster B genes are mainly lipogenic and thermogenic with greater expression in liver of hatchlings. The present study describes the innate chorography of transcriptional responses of liver to the abrupt metabolic switch from aquatic ectothermy (embryos) to free-living endothermy (hatchling chicks).
Publication Title
Transcriptional profiling of liver during the critical embryo-to-hatchling transition period in the chicken (Gallus gallus).
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The majority of NK cells (~90%) are phenotypically characterized as CD56dimCD16+, while the remaining are CD56brightCD16-. The cytotoxic CD56dimCD16+ NK subset expresses higher levels of chemokine receptors, and therefore is preferentially recruited to sites of inflammation. Encounters between CD56dimCD16+ NK cells with target cells and locally secreted inflammatory cytokines synergize to induce activation of this subset, leading to dramatically increased cytotoxic activity against target cells and abundant pro-inflammatory cytokine production often equivalent to that of the CD56brightCD16- population. The early recruitment of activation of CD56dimCD16+ NK cells to sites of inflammation raises many important questions regarding the potential immune functions of these cells that extend beyond their cytotoxic capabilities. This study has sought to elucidate the genetic profile of activated CD56dimCD16+ NK cells via a series of laboratory-based approaches coupled with a bioinformatics persective.
Publication Title
Gene expression profiling of the human natural killer cell response to Fc receptor activation: unique enhancement in the presence of interleukin-12.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 7 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Six DD class GABAergic neurons are generated in the embryo to synapse with ventral muscles and receive input from cholinergic neurons in the dorsal nerve cord. After hatching and toward the end of the first larval (L1) stage, DD neurons reverse polarity (i.e., synapse with dorsal muscles, receive ventral cholinergic inputs). Expression profiles were generated from DD neurons in the early L1 stage before the initiation of the remodeling program.
Publication Title
Transcriptional Control of Synaptic Remodeling through Regulated Expression of an Immunoglobulin Superfamily Protein.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Lin-, CD38-, CD34+ hematopoietic stem cells.
Publication Title
Microarray and serial analysis of gene expression analyses identify known and novel transcripts overexpressed in hematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 268 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The transcriptional responses of human hosts towards influenza viral pathogens are important for understanding virus-mediated immunopathology. Despite great advances gained through studies using model organisms, the complete temporal host transcriptional responses in a natural human system are poorly understood. In a human challenge study using live influenza (H3N2/Wisconsin) viruses, we conducted a clinically uninformed (unsupervised) factor analysis on gene expression profiles and established an ab initio molecular signature that strongly correlates to symptomatic clinical disease. This is followed by the identification of 42 biomarkers whose expression patterns best differentiate early from late phases of infection. In parallel, a clinically informed (supervised) analysis revealed over-stimulation of multiple viral sensing pathways in symptomatic hosts and linked their temporal trajectory with development of diverse clinical signs and symptoms. The resultant inflammatory cytokine profiles were shown to contribute to the pathogenesis because their significant increase preceded disease manifestation by 36 hours. In subclinical asymptomatic hosts, we discovered strong transcriptional regulation of genes involved in inflammasome activation, genes encoding virus interacting proteins, and evidence of active anti-oxidant and cell-mediated innate immune response. Taken together, our findings offer insights into influenza virus-induced pathogenesis and provide a valuable tool for disease monitoring and management in natural environments.
Publication Title
Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 113 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Diagnosis of acute respiratory viral infection is currentlybased on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with viral respiratory infection represents a novel means of infection diagnosis.
Publication Title
Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans.
Sample Metadata Fields
Subject, Time
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. Overall design: DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.
Publication Title
The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.
Sample Metadata Fields
Specimen part, Subject
View Samples