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Briefings in Functional Genomics Advance Access published online on February 12, 2008
Briefings in Functional Genomics, doi:10.1093/bfgp/eln004
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© Oxford University Press, 2008, All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

The plasma proteome, adductome and idiosyncratic toxicity in toxicoproteomics research

B. Alex Merrick

Corresponding author. B. Alex Merrick, Ph.D., National Center for Toxicogenomics, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. Tel: +1 919 541-1531; Fax: +1 919 541-4704; E-mail: merrick{at}niehs.nih.gov

Toxicoproteomics uses the discovery potential of proteomics in toxicology research by applying global protein measurement technologies to biofluids and tissues after host exposure to injurious agents. Toxicoproteomic studies thus far have focused on protein profiling of major organs and biofluids such as liver and blood in preclinical species exposed to model toxicants. The slow pace of discovery for new biomarkers, toxicity signatures and mechanistic insights is partially due to the limited proteome coverage derived from analysis of native organs, tissues and body fluids by traditional proteomic platforms. Improved toxicoproteomic analysis would result by combining higher data density LC-MS/MS platforms with stable isotope labelled peptides and parallel use of complementary platforms. Study designs that remove abundant proteins from biofluids, enrich subcellular structures and include cell specific isolation from heterogeneous tissues would greatly increase differential expression capabilities. By leveraging resources from immunology, cell biology and nutrition research communities, toxicoproteomics could make particular contributions in three inter-related areas to advance mechanistic insights and biomarker development: the plasma proteome and circulating microparticles, the adductome and idiosyncratic toxicity.

Keywords: toxicoproteomics, toxicology, toxicogenomics, biomarkers, mass spectrometry, proteomics, idiosyncratic toxicity, adductome


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