Mass Spectrometry‐Based Proteomics in Systems Toxicology

Advances of proteomics and its application to toxicological studies have led to the development of a new discipline, toxicoproteomics. Toxicoproteomics and its associated technologies are vital for the understanding of toxicity in systems toxicology. Many quantitative proteomic technologies including gel-based and solution-based approaches have been developed. Mass spectrometry is the core technology in proteomics for its capabilities of protein identification and quantification. While global quantitative proteome analysis using either stable isotope labeling or label-free approaches enables the discovery of toxicity biomarkers and toxicity mechanisms, targeted proteomic approaches such as MRM could play important roles in biomarker validation and quantitative analysis of targeted proteins and pathways. To qualify biomarkers for clinical application, biomarker candidates have to be clinically verified and the assay has to be analytically validated. It is essential that quantitative proteomic analysis is eventually conducted in an absolute fashion. Such absolute quantification should be relied on robust stable isotope labeled peptide/protein standards. Keywords: proteomics; 2D-PAGE; mass spectrometry; tandem MS; protein quantitation; stable isotope labeling; biomarker; toxicity mechanism; toxicoproteomics; systems biology