title: Advances in top-down proteomics for disease biomarker discovery.
abstract: 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.
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Calligaris
authors.forename: Claude
authors.initials: C
authors.lastname: Villard
authors.forename: Daniel
authors.initials: D
authors.lastname: Lafitte
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002852:Chromatography, Ion Exchange; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D053858:Metabolic Networks and Pathways; D044085:Microfluidics; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000302:isolation & purification; D040901:Proteomics / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D011506:Proteins