Discovery of biomarker candidates within disease by protein profiling: principles and concepts.
Proteins and peptides present within clinical samples represent a valuable library of information regarding the ongoing processes within cells and tissues in health and disease. We have developed and validated novel technology applications that can be used to characterize the patterns of global protein expression in tissue and biofluids in either gel-based systems or by automated multidimensional nanocapillary liquid chromatography. Mass spectrophotometry platforms using MALDI MS and MS/MS or LTQ ion trap MS were capable of delivering sensitive and accurate identifications of hundreds of proteins contained in individual samples including individual forms of processing intermediates such as phospho peptides. The Systems Biology approach of integrating protein expression data with clinical data such as histopathology, clinical functional measurements, medical imaging scores, patient demographics, and clinical outcome provides a powerful tool for linking biomarker expression with biological processes that can be segmented and linked to disease presentation.
Marko-Varga
György
G
Department of Biological Sciences, AstraZeneca R&D, Lund, Sweden. gyorgy.marko-varga@astrazeneca.com
Lindberg
Henrik
H
Löfdahl
Claes-Göran
CG
Jönsson
Per
P
Hansson
Lennart
L
Dahlbäck
Magnus
M
Lindquist
Eva
E
Johansson
Leif
L
Foster
Martyn
M
Fehniger
Thomas E
TE
D000818:Animals; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002853:Chromatography, Liquid; D030562:Databases, Protein; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis*; D015203:Reproducibility of Results
D015415:Biomarkers; D020543:Proteome