Search results for "Toxicogenomics"
showing 8 items of 8 documents
Use of deep learning methods to translate drug-induced gene expression changes from rat to human primary hepatocytes
2020
In clinical trials, animal and cell line models are often used to evaluate the potential toxic effects of a novel compound or candidate drug before progressing to human trials. However, relating the results of animal and in vitro model exposures to relevant clinical outcomes in the human in vivo system still proves challenging, relying on often putative orthologs. In recent years, multiple studies have demonstrated that the repeated dose rodent bioassay, the current gold standard in the field, lacks sufficient sensitivity and specificity in predicting toxic effects of pharmaceuticals in humans. In this study, we evaluate the potential of deep learning techniques to translate the pattern of …
Transcriptomic study of the toxic mechanism triggered by beauvericin in Jurkat cells
2018
Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5 mu M; 24 h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations. Gene ontology (GO) analysis showed several biological processes related to electron transport chain, oxidative phosphorylation, and cel…
Gene Set to Diseases (GS2D): disease enrichment analysis on human gene sets with literature data
2016
Large sets of candidate genes derived from high-throughput biological experiments can be characterized by functional enrichment analysis. The analysis consists of comparing the functions of one gene set against that of a background gene set. Then, functions related to a significant number of genes in the gene set are expected to be relevant. Web tools offering disease enrichment analysis on gene sets are often based on gene-disease associations from manually curated or experimental data that is accurate but does not cover all diseases discussed in the literature. Using associations automatically derived from literature data could be a cost effective method to improve the coverage of disease…
Herbal Medicines: Boon or Bane for the Human Liver?
2016
Since ages, medicine is the most consistent companion of man. While in primeval time, disease was cured through natural preparations, onset of technology has made today’s formulations synthetic or nature derived. Across the ages, the plausibility of the “savior-turned-slayer” functionality of these drugs remained constant. With the increment in documentation, it becomes evident that many of the commonly used drugs are associated with toxicities. Thus, any drug, irrespective of its origin, needs to be thoroughly assessed. Rampant use of herbal drugs has often been a threat to human health owing to the scarcity in quality assessment. What needs to be understood is that everything natural is n…
Human Embryonic Stem Cell Derived Hepatocyte-Like Cells as a Tool for In Vitro Hazard Assessment of Chemical Carcinogenicity
2011
Hepatocyte-like cells derived from the differentiation of human embryonic stem cells (hES-Hep) have potential to provide a human relevant in vitro test system in which to evaluate the carcinogenic hazard of chemicals. In this study, we have investigated this potential using a panel of 15 chemicals classified as noncarcinogens, genotoxic carcinogens, and nongenotoxic carcinogens and measured whole-genome transcriptome responses with gene expression microarrays. We applied an ANOVA model that identified 592 genes highly discriminative for the panel of chemicals. Supervised classification with these genes achieved a cross-validation accuracy of > 95%. Moreover, the expression of the response g…
Potential of ‘Omics’ Technologies for Implementation in Research on Phytotherapeutical Toxicology
2012
Abstract High toxicity is the most common reason why new agents drop out of drug development in the pharmaceutical industry. There is hope that toxicogenomics facilitates the early detection of toxic effects and their molecular mechanisms of action during preclinical studies to remove potentially toxic substances from the development. Herbal remedies consist of mixtures of different herbs, which represent a considerable source of heterogeneity and toxicity. They may be caused by botanical misidentification, contamination with pesticides, heavy metals, organic solvents, microbials and radioactivity. Intentional faked herbal products may contain chemical drugs or hormones. Approaches to apply…
Toxicogenomics for the prediction of toxicity related to herbs from traditional Chinese medicine.
2010
Toxicogenomics represents the integration of genomics and toxicology to investigate the interaction between genes and environmental stress in human health. It is a scientific field that studies how the genome is involved in responses to environmental stressors and toxicants. The patterns of altered gene expression that are caused by specific exposures or disease outcomes reveal how toxicants may act and cause disease. Nowadays, toxicogenomics faces great challenges in discriminating the molecular basis of toxicity. We do believe that advances in this field will eventually allow us to describe all the toxicological interactions that occur within a living system. Toxicogenomic responses of a …
Evaluation of in vivo and in vitro models of toxicity by comparison of toxicogenomics data with the literature.
2017
Toxicity affecting humans is studied by observing the effects of chemical substances in animal organisms (in vivo) or in animal and human cultivated cell lines (in vitro). Toxicogenomics studies collect gene expression profiles and histopathology assessment data for hundreds of drugs and pollutants in standardized experimental designs using different model systems. These data are an invaluable source for analyzing genome-wide drug response in biological systems. However, a problem remains that is how to evaluate the suitability of heterogeneous in vitro and in vivo systems to model the many different aspects of human toxicity. We propose here that a given model system (cell type or animal o…