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GSE60408
Homo sapiens
863 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Identifying the Mechanism of Action (MoA) of drugs is critical for the development of new drugs, understanding their side effects, and drug repositioning. However, identifying drug MoA has been challenging and has been traditionally attempted only though large experimental setups with little success. While advances in computational power offers the opportunity to achieve this in-silico, methods to exploit existing computational resources are still in their infancy. To overcome this, we developed a novel method to identify Drug Mechanism of Action using Network Dysregulation (DeMAND).
Publication Title
Elucidating Compound Mechanism of Action by Network Perturbation Analysis.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 282 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Analysis of Diffuse Large B-Cell Lymphoma (DLBCL) OCI-LY3 cell line treated with 14 different known drugs at 2 different concentrations and profiled at 6, 12 and 24 hrs after treatment.
Publication Title
A community computational challenge to predict the activity of pairs of compounds.
Sample Metadata Fields
Compound, Time
View Samples- Homo sapiens
- 39 Downloadable Samples
Illumina HiSeq 2000
Description
Transcriptome profiles for innate and adaptive immune stimuli important for host response against mycobacteria. Human monocyte-derived macrophages were stimulated with TLR2/1 ligand and interferon-g, stimuli present during innate and adaptive immune responses, respectively. Overall design: Human monocyte-dervided macrophages from five healthy donors were stimulated with TLR2/1L, IFN-g, or media control for 2, 6, and 24 hours. RNA-sequencing was performed on a total of 45 samples.
Publication Title
S100A12 Is Part of the Antimicrobial Network against Mycobacterium leprae in Human Macrophages.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tuberculosis remains a major cause of death from an infectious disease worldwide, yet only 10% of people infected with Mycobacterium tuberculosis develop disease. Defining both necessary and sufficient immunologic determinants of protection remains a great scientific challenge. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify human potential candidate markers of host defense by studying gene expression profiles of macrophages, cells which, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene co-expression network analysis revealed an association between the cytokine, IL-32, and the vitamin D antimicrobial pathway in a network of IFN- and IL-15 induced defense response genes. IL-32 was sufficient for induction of the vitamin D-dependent antimicrobial peptides, cathelicidin and DEFB4, and generation of antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. The IL-15 induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent vs. active tuberculosis or healthy controls, and a co-expression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15 induced gene network. Inferring that maintaining M. tuberculosis in a latent state and preventing transition to active disease represents host resistance, we believe these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis.
Publication Title
IL-32 is a molecular marker of a host defense network in human tuberculosis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We report the global gene expression of mouse pancreatic cells in a pancreas-specific conditional knock-out mouse for Gata6, as compared with age-matched controls. Total RNA was extracted from the pancreas of 6-8 -week old mice of the two genotypes and analyzed. at this age, Gata6P-/- pancreata are histologically normal, but the acinar differentiation programme is already altered. we observe that loss of Gata6 causes the de-repression of ectopic non-pancreatic genes, as well as some genes involved in the mesenchymal programme. Overall design: mRNA extracted from the pancreas of 4 controls and 4 Gata6P-/- mice was sequenced.
Publication Title
The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integration Analysis of Three Omics Data Using Penalized Regression Methods: An Application to Bladder Cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Omics data integration is becoming necessary to investigate the still unknown genomic mechanisms of complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological mechanisms. To overcome some of these issues, innovative statistical approaches are being developed. In this work, we applied penalized regression methods (LASSO and ENET) to explore relationships between common genetic variants, DNA methylation and gene expression measured in bladder tumor samples and have proposed a permutation-based method to concomitantly assess significance and correct by multiple testing with the MaxT algorithm. The overall analysis flow consisted of three steps: (1) SNPs/CpGs were selected per each gene probe within 1Mb window upstream and downstream the gene; (2) LASSO and ENET were applied to assess the association between each expression probe and the selected SNPs/CpGs in three multivariable models (SNP, CPG, and Global models, the latter integrating SNPs and CPGs); and (3) the significance of each model was assessed using the permutation-based MaxT method. We identified 48 genes whom expression levels were associated with both SNPs and GPGs. Importantly, we replicated results for 36 (75%) of them in an independent data set (TCGA). We checked the performance of the proposed method with a simulation study and further supported our results with a biological interpretation based on an enrichment analysis. The approach we propose allows reducing computational time and is flexibly and easy to implement when analyzing several omics data. Our results highlight the importance of integrating omics data by applying appropriate statistical strategies to discover new insights into the complexity of disease genetic mechanisms.
Publication Title
Integration Analysis of Three Omics Data Using Penalized Regression Methods: An Application to Bladder Cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
BRAF inhibitors are highly effective therapies for patients with BRAF V600 mutated metastatic melanoma. Patients who receive BRAF inhibitors develop a variety of hyper-proliferative skin conditions, whose pathogenic basis is the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyper-proliferative skin changes improve when a MEK inhibitor is co-administered, as a MEK inhibitor blocks paradoxical MAPK activation. We tested whether we could take advantage of the mechanistic understanding of the skin hyper-proliferative side effects of BRAF inhibitors to accelerate skin wound healing by inducing paradoxical MAPK activation. Here we show that the BRAF inhibitor vemurafenib accelerates human keratinocyte proliferation and migration by increasing ERK phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing models in mice accelerated cutaneous wound healing and improved the tensile strength of healing wounds through paradoxical MAPK activation; addition of a MEK inhibitor reversed the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor did not increase the incidence of cutaneous squamous cell carcinomas in mice even after the application of a carcinogen. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds. Overall design: Full depth incisional wound mice tissues with/without Vemurafenib treatment were sent for RNAseq analysis on day 2, 6 and 14
Publication Title
Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
The c-MYC oncogene is a key transcription factor deregulated in most human tumors. Histone marks associated with transcriptionally active genes in euchromatic islands define the set of high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are not known but likely involve chromatin-remodelling and chromatin-modifying complexes. Here, we show that c-MYC interacts with BPTF, a core subunit of the NURF complex that binds active chromatin. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts. BPTF knockdown leads to a decrease in c-MYC recruitment to DNA and to changes in chromatin accessibility. Using BPTF-null MEFs we show that BPTF is necessary for c-MYC-driven proliferation, G1-S progression, and replication stress, but not for c-MYC-driven apoptosis. Consistently, BPTF is required for the proliferation of cells driven by c-MYC, such as Burkitt lymphoma, and its expression in human cancer lines correlates with the activation of c-MYC gene signatures. Our findings point to the c-MYC-BPTF axis as a potential therapeutic target in cancer. Overall design: To assess whether BPTF is required for the transcriptional activity of c-MYC, human foreskin fibroblasts (HFF) were stably transduced with the chimeric MYC-ER cDNA (HFF MYC-ER) and infected with lentiviruses coding for either control (shNt) or BPTF-targeting shRNAs. Cells were serum-starved for 2 days to achieve quiescence and then treated with 4-hydroxytamoxifen (4-OHT)
Publication Title
BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- NextSeq 500
Description
Characterization of gene expression changes in HuH7 HCC cells upon treatment with the Jumonji KDM inhibitor, JIB-04, GSK-J4 and SD-70. Overall design: Comparison of gene expression changes between HuH7 cells treated with JIB-04, GSK-J4 or SD-70 vs. DMSO
Publication Title
A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets.
Sample Metadata Fields
Sex, Age, Treatment, Race, Subject
View Samples