Simultaneous pathway activity inference and global gene expression analysis using RNA-sequencing [halofuginone]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE75209 | GEO | 2016/05/06
SECONDARY ACCESSION(S): PRJNA302808
REPOSITORIES: GEO
Similar Datasets
Project description:Bone marrow derived macrophages treated with small molecules and stimulated with LPS
2016-05-06 | GSE75211 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-05-05 | GSE75212 | GEO
Project description:Two 96-well plates per genotype wild type and Myd88 knockout, 4 hour time series in 0.5 hr increments
2016-05-06 | GSE75210 | GEO
Project description:Simultaneous pathway activity inference and global gene expression analysis using RNA-sequencing
| PRJNA302805 | ENA
Project description:To better understand the interaction of TGFbeta and Toll-like-receptor 4 (TLR4) signaling in monocytes, we performed microarray analysis. We identified a unique set of genes whose expressions in monocytes were regulated by simultaneous stimulation of TLR4 and TGFβ signaling. THP-1 cells, a human monocytic cell line, were stimulated for 24 hours with PBS as control, LPS (100ng/ml), TGFbeta1 (1ng/ml) or LPS (100ng/ml) + TGFbeta1 (1ng/ml). After 24 hours of stimulation, total RNA was isolated and prepared for genome wide analyses using Illumina HumanRef8 V3.0 Beadchips. In total 32 arrays were analyzed including 8 samples of PBS-stimulated monocytes, 8 samples of LPS-stimulated monocytes, 8 samples of TGFbeta1 stimulated monocytes and 8 samples of monocytes stimulated with LPS + TGFbeta1.
2012-12-15 | E-GEOD-17909 | biostudies-arrayexpress
Project description:Reporter gene assays are a venerable tool for studying signaling pathways, but they lack the throughput and complexity necessary to contribute to a systems-level understanding of endogenous signaling networks. We present a parallel reporter assay, transcription factor activity sequencing (TF-seq), built on synthetic DNA enhancer elements, which enables parallel measurements in primary cells of the transcriptome and transcription factor activity from more than 40 signaling pathways. Using TF-seq in Myd88(-/-) macrophages, we captured dynamic pathway activity changes underpinning the global transcriptional changes of the innate immune response. We also applied TF-seq to investigate small molecule mechanisms of action and find a role for NF-κB activation and coordination of the STAT1 response in the macrophage reaction to the anti-inflammatory natural product halofuginone. Simultaneous TF-seq and global gene expression profiling represent an integrative approach for gaining mechanistic insight into pathway activity and transcriptional changes that result from genetic and small molecule perturbations.
| S-EPMC5032147 | biostudies-literature
Project description:Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactions and modifications to indirect regulatory relationships. One goal of systems biology is to bridge three aspects of this complexity: the growing body of high-throughput data assaying these interactions; the specific interactions in which individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data. This results in a comprehensive compendium of whole-genome networks for yeast, derived from ?3,500 experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory) to specific (e.g. phosphorylation or transcriptional regulation). We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel connection between glycogen breakdown and glucose utilization supported by recent publications. Additionally, 14 specific predicted interactions in DNA topological change and protein biosynthesis were experimentally validated. We analyzed the systems-level network features within all interactomes, verifying the presence of small-world properties and enrichment for recurring network motifs. This compendium of physical, synthetic, regulatory, and functional interaction networks has been made publicly available through an interactive web interface for investigators to utilize in future research at http://function.princeton.edu/bioweaver/.
| S-EPMC2991250 | biostudies-literature
Project description:In this research, we use DNA microarray analysis to clarify the gene expression responses from thalidomide in PBMC cells after lipopolysaccharide (LPS) treatment. Analysis used PBMC as control samples for comparison to the experimental samples: PBMC stimulated with LPS and PBMC stimulated with LPS treated with LPS. Indirect comparisons were made across multiple arrays with raw data pulled from different channels for data analysis and comparison to the control data.
2011-09-29 | E-GEOD-28708 | biostudies-arrayexpress
Project description:BackgroundRecent in vivo studies showed new hopes of drug repositioning through causality inference from drugs to disease. Inspired by their success, here we present an in silico method for building a causal network (CauseNet) between drugs and diseases, in an attempt to systematically identify new therapeutic uses of existing drugs.MethodsUnlike the traditional 'one drug-one target-one disease' causal model, we simultaneously consider all possible causal chains connecting drugs to diseases via target- and gene-involved pathways based on rich information in several expert-curated knowledge-bases. With statistical learning, our method estimates transition likelihood of each causal chain in the network based on known drug-disease treatment associations (e.g. bexarotene treats skin cancer).ResultsTo demonstrate its validity, our method showed high performance (AUC = 0.859) in cross validation. Moreover, our top scored prediction results are highly enriched in literature and clinical trials. As a showcase of its utility, we show several drugs for potential re-use in Crohn's Disease.ConclusionsWe successfully developed a computational method for discovering new uses of existing drugs based on casual inference in a layered drug-target-pathway-gene- disease network. The results showed that our proposed method enables hypothesis generation from public accessible biological data for drug repositioning.
| S-EPMC3853312 | biostudies-literature
Project description:Medicinal plants have shown great promise as a source of novel drug compounds for the treatment of inflammatory disorders. In our search for new entities with anti-inflammatory potential, the extracts of the whole plant of Saussurea heteromalla (family-Asteraceae), collected from Himalayas, were evaluated in the high throughput screen for TNF-α and IL-6 inhibitors. The plant has been found as a new source of chlorojanerin, a guaianolide type of sesquiterpene lactone. This is the first report on the potent anti-inflammatory activity of the compound. Chlorojanerin was shown to be significantly effective in inhibiting TNF-α and IL-6 production in LPS induced THP-1 cells (TNF-α, IC50 = 3µM and IL-6, IC50 = 0.8µM). The compound also blocked TNF-α and IL-6 production from LPS induced human monocytes and synovial cells from RA patients. Chlorojanerin also inhibited the binding of NF-κB in a GFP reporter assay system. Transcriptional profiling of the LPS stimulated THP-1 cells revealed that chlorojanerin exerted its anti-inflammatory effect by inhibiting the expression of genes involved in activating the transcription factor – NF-κB. Real time analysis of these genes validated the effect of chlorojanerin on the classical downstream targets of NF-κB. Thus, this study clearly delineated 8 targets specific for the effect of chlorojanerin on NF-κB induced signaling at the mRNA level. This work is a step towards the isolation and characterization of lead anti-inflammatory agents from the extract of Saussurea heteromalla, which can be developed into better therapeutic molecules targeted towards some specific inflammatory diseases. Single dye labelling with Cy3 for all treatment RNA samples. Treatments included unstimulated, LPS stimulated, Chlorjanerin treatment and dexamethasone treatment.
2011-12-14 | E-GEOD-34180 | biostudies-arrayexpress