Utilizing Human Blood Plasma for Proteomic Biomarker Discovery

Candidate proteomic biomarker discovery from human plasma holds both incredible clinical potential as well as significant challenges. The dynamic range of proteins within plasma is known to exceed 1010, and many potential biomarkers are likely present at lower protein abundances. At present, proteom...

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Bibliographic Details
Published in:Journal of proteome research 2005-07, Vol.4 (4), p.1073-1085
Main Authors: Jacobs, Jon M, Adkins, Joshua N, Qian, Wei-Jun, Liu, Tao, Shen, Yufeng, Camp, David G, Smith, Richard D
Format: Article
Language:English
Subjects:
Biomarkers - blood
Humans
Mass Spectrometry - methods
Plasma - chemistry
Proteome - analysis
Proteomics - methods
Statistics as Topic
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Summary:Candidate proteomic biomarker discovery from human plasma holds both incredible clinical potential as well as significant challenges. The dynamic range of proteins within plasma is known to exceed 1010, and many potential biomarkers are likely present at lower protein abundances. At present, proteomic based MS analyses provide a dynamic range typically not exceeding ∼103 in a single spectrum, and ∼104−106 when combined with on-line separations (e.g., reversed-phase gradient liquid chromatography), and thus are generally insufficient for low level biomarker detection directly from human plasma. This limitation is providing an impetus for the development of experimental methodologies and strategies to increase the possible number of detections within this biofluid. Discussed is the diversity of available approaches currently used by our laboratory and others to utilize human plasma as a viable medium for biomarker discovery. Various separation, depletion, enrichment, and quantitative efforts as well as recent improvements in MS capabilities have resulted in measurable improvements in the detection and identification of lower abundance proteins (by ∼10−102). Despite these improvements, further advances are needed to provide a basis for discovery of candidate biomarkers at very low levels. Continued development of depletion and enrichment techniques, coupled with improved pre-MS separations (both at the protein and peptide level) holds promise in extending the dynamic range of proteomic analysis. Keywords: biomarker • plasma • serum • human • proteomics • mass spectrometry • MS
ISSN:1535-3893
1535-3907
DOI:10.1021/pr0500657