Investigating Diversity in Human Plasma Proteins

Plasma proteins represent an important part of the human proteome. Although recent proteomics research efforts focus largely on determining the overall number of proteins circulating in plasma, it is equally important to delineate protein variations among individuals, because they can signal the ons...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 102; no. 31; pp. 10852 - 10857
Main Authors Nedelkov, Dobrin, Kiernan, Urban A., Niederkofler, Eric E., Tubbs, Kemmons A., Nelson, Randall W., Cantor, Charles R.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 02.08.2005
National Acad Sciences
Subjects
Adolescent
Adult
Aged
Amyloids
Average linear density
Biochemistry
Biological Sciences
Blood proteins
Blood Proteins - chemistry
Blood Proteins - genetics
Blood Proteins - metabolism
Cohort Studies
Cystatins
Female
Genetic diversity
Genetic Markers
Genetic Variation
Genetics, Population
Humans
Male
Mass spectra
Mass Spectrometry
Middle Aged
Pipettes
Point Mutation
Population genetics
Protein Processing, Post-Translational
Proteins
Proteomics
Transferrins
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Summary:Plasma proteins represent an important part of the human proteome. Although recent proteomics research efforts focus largely on determining the overall number of proteins circulating in plasma, it is equally important to delineate protein variations among individuals, because they can signal the onset of diseases and be used as biological markers in diagnostics. To date, there has been no systematic proteomics effort to characterize the breadth of structural modifications in individual proteins in the general population. In this work, we have undertaken a population proteomics study to define gene- and protein-level diversity that is encountered in the general population. Twenty-five plasma proteins from a cohort of 96 healthy individuals were investigated through affinity-based mass spectrometric assays. A total of 76 structural forms/variants were observed for the 25 proteins within the samples cohort. Posttranslational modifications were detected in 18 proteins, and point mutations were observed in 4 proteins. The frequency of occurrence of these variations was wide-ranged, with some modifications being observed in only one sample, and others detected in all 96 samples. Even though a relatively small cohort of individuals was investigated, the results from this study illustrate the extent of protein diversity in the human population and can be of immediate aid in clinical proteomics/biomarker studies by laying a basal-level statistical foundation from which protein diversity relating to disease can be evaluated.
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Abbreviations: HBS, Hepes-buffered saline; SAA, serum amyloid A.
To whom correspondence may be addressed. E-mail: dnedelkov@intrinsicbio.com or rnelson@intrinsicbio.com.
This paper was submitted directly (Track II) to the PNAS office.
Edited by Charles R. Cantor, Sequenom, Inc., San Diego, CA
Author contributions: D.N. designed research; D.N., U.A.K., E.E.N., K.A.T., and R.W.N. performed research; K.A.T. contributed new reagents/analytic tools; D.N., U.A.K., E.E.N., and R.W.N. analyzed data; and D.N. and R.W.N. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0500426102