The plasma proteome, adductome and idiosyncratic toxicity in toxicoproteomics research

Toxicoproteomics uses the discovery potential of proteomicsin toxicology research by applying global protein measurementtechnologies to biofluids and tissues after host exposure toinjurious agents. Toxicoproteomic studies thus far have focusedon protein profiling of major organs and biofluids such as liverand blood in preclinical species exposed to model toxicants.The slow pace of discovery for new biomarkers, toxicity signaturesand mechanistic insights is partially due to the limited proteomecoverage derived from analysis of native organs, tissues andbody fluids by traditional proteomic platforms. Improved toxicoproteomicanalysis would result by combining higher data density LC-MS/MSplatforms with stable isotope labelled peptides and paralleluse of complementary platforms. Study designs that remove abundantproteins from biofluids, enrich subcellular structures and includecell specific isolation from heterogeneous tissues would greatlyincrease differential expression capabilities. By leveragingresources from immunology, cell biology and nutrition researchcommunities, toxicoproteomics could make particular contributionsin three inter-related areas to advance mechanistic insightsand biomarker development: the plasma proteome and circulatingmicroparticles, the adductome and idiosyncratic toxicity.