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J Proteomics. 2011 Jun 10;74(7):920-34. doi: 10.1016/j.jprot.2011.03.030. Epub 2011 Apr 6.

Advances in top-down proteomics for disease biomarker discovery.

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INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Aix-Marseille Université, Plateforme Protéomique et Innovation Technologique Timone, Faculté de Pharmacie, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 5, France.


Top-down mass spectrometry strategies allow identification and characterization of proteins and protein networks by direct fragmentation. These analytical processes involve a panel of fragmentation mechanisms, some of which preserve protein post-translational modifications. Thus top-down is of special interest in clinical biochemistry to probe modified proteins as potential disease biomarkers. This review describes separating methods, mass spectrometry instrumentation, bioinformatics, and theoretical aspects of fragmentation mechanisms used for top-down analysis. The biological interest of this strategy is extensively reported regarding the characterization of post-translational modifications in biochemical pathways and the discovery of biomarkers. One has to bear in mind that quantitative aspects that are beyond the focus of this review are also of critical important for biomarker discovery. The constant evolution of technologies makes top-down strategies crucial players in clinical and basic proteomics.

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