The emergence of top-down proteomics in clinical research

Table 1 Selected applications of intact protein analysis in translational research

Laboratory^a	Disease or condition	Application description	Reference
Chamot-Rooke	Bacterial meningitis	Relative quantification of intact Neisseria meningitidis type IV pilus proteoforms	[33]
Agar	Neurodegeneration	H-D exchange-enabled analysis of fALS SOD1 variant protein dynamics	[36]
Ge	Myocardial dysfunction	Relative quantification of intact cardiac troponin I proteoforms	[34]
Caprioli	Renal carcinoma	Tissue profiling of intact proteins in cancerous versus healthy kidneys	[32]
Hendrickson and Yates	Coronary artery disease	Relative quantification of intact apolipoprotein CIII proteoforms	[35]
Nelson	Diabetes	Relative quantification of proteoforms in plasma from healthy individuals and diabetics	[41]

^aExamples of laboratories applying top-down proteomic strategies to clinically related research are presented here, with references to their recent work. In this diverse research, top-down proteomics is being used to understand the dynamics of intact proteins, to measure the relative abundances of intact proteoforms and to provide mass spectrometry profiles of intact proteins directly from human tissue. In all of these cases, the information obtained by studying whole proteins has led to significant insight into human disease. fALS, familial amyotrophic lateral sclerosis; H-D, hydrogen-deuterium; SOD1, superoxide dismutase 1.

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