Toxicogenomics
From DrugPedia: A Wikipedia for Drug discovery
Toxicogenomics is a field of science that deals with the collection, interpretation, and storage of information about gene and protein activity within particular cell or tissue of an organism in response to toxic substances. Toxicogenomics meshes toxicology with genomics or molecular profiling, i.e. transcriptomics, proteomics and metabonomics<ref>The National Academies Press: Communicating Toxicogenomics Information to Nonexperts: A Workshop Summary (2005) [1]</ref><ref>Toxicogenomics: Principles and Applications; Ed.: H. K. Hamadeh and C. A. Afshari; Hoboken, NJ:Wiley-Liss, 2004. 361 pp. ISBN: 0-471-43417-5 [2]</ref>.
This broad definition is supported by the United States Environmental Protection Agency stating that "the term "genomics" encompasses a broader scope of scientific inquiry and associated technologies than when genomics was initially considered. A genome is the sum total of all an individual organism's genes. Thus, genomics is the study of all the genes of a cell, or tissue, at the DNA (genotype), mRNA (transcriptome), or protein (proteome) levels. Genomics methodologies are expected to provide valuable insights for evaluating how environmental stressors affect cellular/tissue function and how changes in gene expression may relate to adverse effects. However, the relationships between changes in gene expression and adverse effects are unclear at this time and may likely be difficult to elucidate."<ref>EPA Interim Genomics Policy [3]</ref>
The nature and complexity of the data (in volume and variability) demands highly dvelopped processes for of automated handling and storage. The analysis usually involves a wide array of bioinformatics and statistics.<ref>Mattes et al. Environ Health Perspect. 2004 Mar;112(4):495-505 [4]</ref>, regularly involving classification approaches<ref>Ellinger-Ziegelbauer et al., Mutat Res. 2008 Jan 1;637(1-2):23-39 [5]</ref>.
In pharmaceutical Drug discovery and development toxicogenomics is used to study adverse, i.e. toxic, effects, of pharmaceutical drugs in defined model systems in order to draw conclusions on the toxic risk to patients or the environment. Both the EPA and the U.S. Food and Drug Administration currently preclude basing regulatory decision making on genomics data alone. However, they do encourage the voluntary submission of well-documented, quality genomics data. Both agencies are considering the use of submitted data on a case-by-case basis for assessment purposes (e.g., to help elucidate mechanism of action or contribute to a weight-of-evidence approach) or for populating relevant comparative databases by encouraging parallel submissions of genomics data and traditional toxicologic test results.<ref>Environ Health Perspect. 2006 March; 114(3): 420–429 [6]</ref>
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[edit] Public Toxicogenomics Projects
- Chemical Effects in Biological Systems (CEBS) - Project hosted by the National Institute of Environmental Health Sciences (NIEHS) building a knowledgebase of toxicology studies including study design, clinical pathology, and histopathology and toxicogenomics data.<ref>Collins et al., Expert Opin. Drug Metab. Toxicol. (2007) 3(5):689-704 [7]</ref>
- InnoMed PredTox assessing the value of combining results from omics technologies together with the results from more conventional toxicology methods in more informed decision making in preclinical safety evaluation.<ref>W.B. Mattes: Methods Mol Biol. 2008;460:221-38. [8]</ref>
- Predictive Safety Testing Consortium aiming to identify and clinically qualify safety biomarkers for regulatory use as part of the FDA's Critical Path Initiative<ref>W.B. Mattes: Methods Mol Biol. 2008;460:221-38. [9]</ref>
- ToxCast program for Predicting Hazard, Characterizing Toxicity Pathways, and Prioritizing the Toxicity Testing of Environmental Chemicals at the United States Environmental Protection Agency<ref>Dix et al., Toxicol Sci. 2007 Jan;95(1):5-12[10]</ref>
[edit] References
[edit] See also
[edit] External links
- Comparative Toxicogenomics Database - a public database that integrates toxicogenomic data for chemicals, genes, and diseases from the scientific literature.
Center for Research on Occupational and Environmental Toxicology definition by the CROET Research Centers: (Neuro)toxicogenomics and Child Health Research Center.
- InnoMed PredTox - official project website
- ToxCast - official project website
