Similar Datasets
Project description:Protein expression signatures of a PromoCell cardiomyocyte with drug-induced toxicity and toxicity mitigation by multiple drugs.
2016-01-04 | LDS-1266 | LINCS
Project description:In summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Addiction, Drugs of abuse, Time-course, Immediate Early Genes, Glucocorticoid receptor dependent genes, Cocaine, Heroin, Nicotine, Ethanol, Morphine, Methamphetamine
2010-04-14 | GSE15774 | GEO
Project description:In summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Addiction, Drugs of abuse, Time-course, Immediate Early Genes, Glucocorticoid receptor dependent genes, Cocaine, Heroin, Nicotine, Ethanol, Morphine, Methamphetamine The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Six the most addictive and harming drugs of abuse (morphine 20 mg/kg, heroin 10 mg/kg, ethanol 2 g/kg, nicotine 1 mg/kg, methamphetamine 2 mg/kg or cocaine 25 mg/kg, i.p.) were selected for the comparison. Drug doses were previously reported as rewarding in mice and further tested in our laboratory. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naïve animals were prepared for each time point. Design of the experiment assumed pooling of two animals per each array and using of three independent arrays per group. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.
2010-04-14 | E-GEOD-15774 | biostudies-arrayexpress
Project description:The intestine is an organ responsible for absorption and metabolism of orally administered drugs. It is necessary to examine the human intestinal expression profiles of the genes related to drug absorption, distribution, metabolism, and excretion (ADME), for accurate prediction of pharmacokinetics in the intestine. However, previous studies had issues such as the evaluation limited to specific molecules and regions, and relatively small sample sizes. In this study, to obtain more accurate expression profiles of mRNA and protein in various regions of human intestine, biopsy samples were collected from 38 patients with various regions, duodenum, jejunum, ileum, colon and rectum, and RNA-seq analysis and quantitative proteomics analysis were performed. We performed the expression analysis of drug-metabolizing enzymes (cytochromes P450 (CYP ) and non–CYP enzymes), apical and basolateral drug transporters, and nuclear receptors. Overall, mRNA expression levels of these ADME-related molecules were highly correlated with the protein expression levels. The characteristics of the expression of ADME-related genes in human small and large intestines differed significantly, such as higher or lower expression levels of CYP enzymes in the small or large intestines, respectively. Most CYPs were expressed dominantly in the small intestine. Non-CYPs were expressed in the large intestine, but their expression levels were lower than those in the small intestine. The expression levels of ADME-related genes differed even between the proximal and distal small intestine. The expression of transporters showed their highest abundance in the ileum. The data in the present study contributes to an improved understanding of intestinal ADME of drug candidates, and would be useful for drug discovery research.
2023-05-08 | GSE215285 | GEO
Project description:Ribosome profiling is a widespread tool for studying translational dynamics in human cells. Its central assumption is that ribosome footprint density on a transcript quantitatively reflects protein synthesis. Here, we test this assumption using pulsed-SILAC (pSILAC) high-accuracy targeted proteomics. We focus on multiple myeloma cells exposed to bortezomib, a first-line chemotherapy and proteasome inhibitor. In the absence of drug effects, we found that direct measurement of protein synthesis by pSILAC correlated well with indirect measurement of synthesis from ribosome footprint density. This correlation, however, broke down under bortezomib-induced stress. By developing a statistical model integrating longitudinal proteomic and mRNA-seq measurements, we found that proteomics could directly detect global alterations in translational rate caused by bortezomib; these changes are not detectable by ribosomal profiling alone. Further, by incorporating pSILAC data into a gene expression model, we predict cell-stress specific proteome remodeling events. These results demonstrate that pSILAC provides an important complement to ribosome profiling in measuring proteome dynamics. Timecourse experiment with six points over 48hr after bortezomib exposure in MM.1S myeloma cells. mRNA-seq and ribosome profiling data at each time point.
2017-05-18 | E-GEOD-69047 | biostudies-arrayexpress
Project description:Lysine deacetylase inhibitors (KDACis) are approved drugs for cutaneous T-cell lymphoma (CTCL) and multiple myeloma. The drugs lead to increasing acetylation levels of histones and other proteins, altered gene expression, and cell death. To characterize the mechanisms of action of these drugs in more detail, we systematically measured dose-dependent drug-induced changes in protein expression, acetylation, and phosphorylation in response to 21 clinical and pre-clinical KDACis. The resulting 872,000 dose-response curves revealed, for instance, poor selectivity of HDAC1, 2, 3, and 6 inhibitors in cells, strong cross-talk between acetylation and phosphorylation pathways, localization of most drug-responsive acetylation sites to intrinsically disordered regions (IDRs), an underappreciated role of acetylation in protein structure and a shift in EP300 protein abundance between the cytoplasm and the nucleus. This comprehensive dataset serves as a resource for the investigation of the molecular mechanisms underlying KDACi action in cells and can be explored online in ProteomicsDB.
2024-04-21 | PXD047419 | panorama
Project description:Hepatocellular carcinoma (HCC) is a complex and deadly disease lacking druggable genetic mutations. The limited efficacy of systemic treatments for advanced HCC implies that novel predictive biomarkers and drug targets are urgently needed. Most HCC drugs target protein kinases and their kinase-dependent signaling networks to drive HCC progression. To identify HCC signaling networks that determine responses to kinase inhibitors (KIs), we apply a pharmacoproteomics approach integrating kinome activity in 17 HCC cell lines with their responses to 299 KIs, resulting in a comprehensive dataset of pathway-based drug response signatures. By profiling patient HCC samples, we identify signatures of clinical HCC drug responses in individual tumors. Our analyses reveal kinase networks promoting the epithelial-mesenchymal transition (EMT) and drug resistance, including a FZD2-AXL-NUAK1/2 signaling module, whose inhibition reverses the EMT and sensitizes HCC cells to drugs. Our approach identifies cancer drug targets and molecular signatures of drug response for personalized oncology.
2018-12-15 | MSV000083236 | MassIVE
Project description:Chronic inflammation plays a critical role in the initiation and development of various human illnesses. The use of steroidal anti-inflammatory drugs (SAIDs) or non-steroidal anti-inflammatory drugs (NSAIDs) is now much more frequent and presents a number of unwanted side effects. For example long- or short-term usage of SAIDs presents multiple negative side effects such as stomach irritation, thinning of the skin, immune defence regression, weight gain and even sometimes a cortico-dependence, and NSAIDs have been linked to a higher risk of strokes, heart attacks, and heart-related deaths. In parallel, there has been renewed interest in alternative medicines and natural therapies and thousands of potential medicinal plants, including sage and chamomile. This study assesses the gene expression responses of human mature adipopcytes (differentiated from fibroblastic pre-adipocytes [PromoCell, Germany; Catalogue #C-12730]), pre-treated with aqueous ethanol extract of sage (Salvia officinalis) or Roman chamomile (Chamaemelum nobile), following 4h or 24h treatment with IL-1B versus control conditions.
2020-10-05 | E-MTAB-9609 | biostudies-arrayexpress
Project description:Drug Toxicity Signature Generation Center (DToxS) at the Icahn School of Medicine at Mount Sinai is an integral part of the NIH Library of Integrated Network-Based Cellular Signatures (LINCS) program. A key aim of DToxS is to generate both proteomic and transcriptomic signatures that cab predict adverse effects, especially cardiotoxicity, of drugs approved by the Food and Drug Administration. Towards this goal, high throughput shot-gun proteomics experiments (308 cell line/drug combinations + 64 HeLa control lysates + 9 auxiliary treatment samples) have been conducted at the Center for Advanced Proteomics Research at Rutgers-New Jersey Medical School. The integrated proteomic and transcriptomic signatures have been used for computational network analysis to identify cellular signatures of cardiotoxicity that may predict drug-induced toxicity and possible mitigation of such toxicities by mixing different drugs. Both raw and processed proteomics data have been carefully controlled for quality and have been made publicly available via the PRoteomics IDEntifications (PRIDE) database. As such, this broad drug-stimulated proteomic dataset is valuable for the prediction drug toxicities and their mitigation.
2021-10-18 | PXD014791 | Pride
Project description:Gene expression signatures for IhhN protein induced cells
| PRJNA298758 | ENA