Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Investigating diversity in human plasma proteins

Dobrin Nedelkov, Urban A. Kiernan, Eric E. Niederkofler, Kemmons A. Tubbs, and Randall W. Nelson
PNAS August 2, 2005 102 (31) 10852-10857; https://doi.org/10.1073/pnas.0500426102
Dobrin Nedelkov
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Urban A. Kiernan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric E. Niederkofler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kemmons A. Tubbs
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Randall W. Nelson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  1. Edited by Charles R. Cantor, Sequenom, Inc., San Diego, CA (received for review January 18, 2005)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Abstract

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.

  • mass spectrometry
  • population proteomics
  • protein modifications

Footnotes

  • ↵ * To whom correspondence may be addressed. E-mail: dnedelkov{at}intrinsicbio.com or rnelson{at}intrinsicbio.com.

  • 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.

  • This paper was submitted directly (Track II) to the PNAS office.

  • Abbreviations: HBS, Hepes-buffered saline; SAA, serum amyloid A.

  • ↵ † It is highly unlikely that the observed protein modifications are a byproduct of the extraction process, because the purification conditions employed in the assay were essentially those traditionally used in protein purification by using immunoprecipitation. It is possible that some of the oxidized protein forms were enhanced by prolonged sample storage at -75°C, but most of the modifications observed here have also been detected in fresh nonfrozen plasma samples (8, 11, 17-20).

  • ↵ ‡ Seven proteins, albumin, cerruloplasmin, C-reactive protein, insulin-like growth factor I, lysozyme, plasminogen, and urine protein 1, were not observed to exhibit any modifications, as indicated by the absence of any other peaks in the mass spectra except for the wild-type protein signal. That is not to say that there were not, in fact, any modifications present in these proteins, especially in albumin, plasminogen, and ceruloplasmin. It should be noted that the method we utilized detailed peptide mapping experiments only in those samples where visible deviations from the wild-type molecular mass were observed in the mass spectra. Because all three of the above-mentioned proteins are high molecular mass proteins, glycosylated (plasminogen and ceruloplasmin), and highly heterogeneous (albumin), the resulting wild-type signals in the mass spectra are relatively wide and of reduced resolution, making the observation of small mass shifts resulting from, e.g., single amino acid substitution, extremely difficult to delineate from the native mass signals.

  • ↵ § The mass spectra resulting from these plasma assays were dominated by signals from the targeted protein. In few instances, signals from nonspecifically bound (to the support) apolipoprotein Cs appeared in the mass spectra. These few additional peaks do not interfere with the overall analysis, as long as their existence is acknowledged and their character (m/z value) is known. Moreover, they can be used advantageously to internally calibrate the mass spectra for a more accurate m/z peak assignment.

  • Freely available online through the PNAS open access option.

  • Copyright © 2005, The National Academy of Sciences
View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Investigating diversity in human plasma proteins
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
Citation Tools
Investigating diversity in human plasma proteins
Dobrin Nedelkov, Urban A. Kiernan, Eric E. Niederkofler, Kemmons A. Tubbs, Randall W. Nelson
Proceedings of the National Academy of Sciences Aug 2005, 102 (31) 10852-10857; DOI: 10.1073/pnas.0500426102

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Investigating diversity in human plasma proteins
Dobrin Nedelkov, Urban A. Kiernan, Eric E. Niederkofler, Kemmons A. Tubbs, Randall W. Nelson
Proceedings of the National Academy of Sciences Aug 2005, 102 (31) 10852-10857; DOI: 10.1073/pnas.0500426102
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 116 (49)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results and Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Modulating the body's networks could become mainstream therapy for many health issues. Image credit: The Feinstein Institutes for Medicine Research.
Core Concept: The rise of bioelectric medicine sparks interest among researchers, patients, and industry
Modulating the body's networks could become mainstream therapy for many health issues.
Image credit: The Feinstein Institutes for Medicine Research.
Adaptations in heart structure and function likely enabled endurance and survival in preindustrial humans. Image courtesy of Pixabay/Skeeze.
Human heart evolved for endurance
Adaptations in heart structure and function likely enabled endurance and survival in preindustrial humans.
Image courtesy of Pixabay/Skeeze.
Viscoelastic carrier fluids enhance retention of fire retardants on wildfire-prone vegetation. Image courtesy of Jesse D. Acosta.
Viscoelastic fluids and wildfire prevention
Viscoelastic carrier fluids enhance retention of fire retardants on wildfire-prone vegetation.
Image courtesy of Jesse D. Acosta.
Water requirements may make desert bird declines more likely in a warming climate. Image courtesy of Sean Peterson (photographer).
Climate change and desert bird collapse
Water requirements may make desert bird declines more likely in a warming climate.
Image courtesy of Sean Peterson (photographer).
QnAs with NAS member and plant biologist Sheng Yang He. Image courtesy of Sheng Yang He.
Featured QnAs
QnAs with NAS member and plant biologist Sheng Yang He
Image courtesy of Sheng Yang He.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Classics
  • Front Matter
  • Teaching Resources
  • Anthropology
  • Chemistry
  • Physics
  • Sustainability Science

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2019 National Academy of Sciences. Online ISSN 1091-6490