Discovering human protein diversity

Authors

  • Dobrin Nedelkov Institute for Population Proteomics and Intrinsic Bioprobes Inc. 2155 E. Conference Dr. Suite 104, Tempe, AZ 85284

DOI:

https://doi.org/10.20450/mjcce.2008.229

Keywords:

protein diversity, population proteomics, protein isoforms, plasma, serum, mass spectrometry, immunoassay

Abstract

Current emphasis on discovering and correlating human genetic variations lays the foundation for future studies of human protein diversity. Protein posttranslational processing, along with the translation of genetic variations, results in a complex, variable human proteome. Analyzing these protein variations on a grandeur scale has become feasible with the advent of mass spectrometry. Mass spectrometry is the only detection method today that can universally provide information about specific protein structural modifications, without a priori knowledge of the modification. However, high-throughput separation approaches are needed to effectively prepare the proteins for mass spectrometric interrogation. Such are the immunoaffinity separations that target single proteins by using highly specific antibodies for their affinity retrieval from the biological fluids. The resulting combination of immunoaffinity separation with MALDI-TOF mass spectrometry, termed Mass Spectrometric Immunoassay (MSIA), has been recently applied in two large studies of protein diversity. The results of these studies reveal a human protein diversity that is far more complex than the variations observed at the genetic level. Assessing the human proteome variations among and within populations will be an important future undertaking with significant clinical and diagnostic implications.

References

E. S. Lander et al., Initial sequencing and analysis of the human genome. Nature, 409, 860–921(2001).

J. C. Venter et al., The sequence of the human genome. Science, 291, 1304–1351(2001).

D. Altshuler et al., A haplotype map of the human genome. Nature, 437, 1299–1320 (2005).

D. A. Wheeler et al., The complete genome of an individual by massively parallel DNA sequencing. Nature, 452, 872–876 (2008).

S. Levy et al., The diploid genome sequence of an individual human. PLoS Biol, 5, e254 (2007).

J. M. Kidd et al., Mapping and sequencing of structural variation from eight human genomes. Nature, 453, 56-64 (2008).

J. Kaiser, DNA sequencing. A plan to capture human diversity in 1000 genomes. Science, 319, 395 (2008).

E. Pennisi, Breakthrough of the year. Human genetic variation. Science, 318, 1842–1843 (2007).

D. M. Behar, S. Rosset, J. Blue-Smith, O. Balanovsky, S. Tzur, D. Comas, R. J. Mitchell, L. Quintana-Murci, C. Tyler-Smith, R. S. Wells, The Genographic project public participation mitochondrial DNA database. PLoS Genet 3, e104 (2007).

R. M. Lequin, Enzyme immunoassay (EIA)/enzymelinked immunosorbent assay (ELISA). Clin. Chem., 51, 2415–2418 (2005).

W. Y. Craig, T. B. Ledue, R. F. Ritchie, Plasma Proteins: Clinical Utility and Interpretation, Foundation for Blood Research, Scarborough, ME 2001.

R. F. Ritchie (Ed.), Serum Proteins in Clinical Medicine, Foundation for Blood Research, Scarborough, ME 1999.

R. Aebersold, M. Mann, Mass spectrometry-based proteomics. Nature, 422, 198–207 (2003).

B. F. Cravatt, G. M. Simon, J. R.Yates, 3rd, The biological impact of mass-spectrometry-based proteomics. Nature, 450, 991–1000 (2007).

D. Nedelkov, Mass spectrometry-based immunoassays for the next phase of clinical applications. Expert Rev Proteomics, 3, 631–640 (2006).

R. W. Nelson, J. R. Krone, A. L. Bieber, P. Williams, Mass-spectrometric immunoassay. Anal. Chem. 67, 1153 –1158 (1995).

D. Nedelkov, U. A. Kiernan, E. E. Niederkofler, K. A. Tubbs, R. W. Nelson, Investigating diversity in human plasma proteins. Proc. Natl. Acad. Sci. U S A, 102, 10852–10857 (2005).

L. H. Connors, A. Lim, T. Prokaeva, V. A. Roskens, C. E. Costello, Tabulation of human transthyretin (TTR) variants, Amyloid, 10, 160–184 (2003).

D. Nedelkov, D. A. Phillips, K. A. Tubbs, R. W. Nelson, Investigation of human protein variants and their frequency in the general population. Mol. Cell. Proteomics, 6, 1183–1187 (2007).

D. Nedelkov, Population proteomics: addressing protein diversity in humans. Expert Rev. Proteomics, 2, 315–324 (2005).

D. Nedelkov, Population proteomics: investigation of protein diversity in human populations. Proteomics, 8, 779–786 (2008).

D. Nedelkov, U. A. Kiernan, E. E. Niederkofler, K. A. Tubbs, R. W. Nelson, Population proteomics: the cConcept, attributes, and potential for cancer biomarker research. Mol Cell Proteomics, 5, 1811–1818 (2006).

Downloads

Published

2008-12-15

How to Cite

Nedelkov, D. (2008). Discovering human protein diversity. Macedonian Journal of Chemistry and Chemical Engineering, 27(2), 99–106. https://doi.org/10.20450/mjcce.2008.229

Issue

Vol. 27 No. 2 (2008)

Section

Biotechnology

License

The authors agree to the following licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

  • Adapt — remix, transform, and build upon the material
  • for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.

 Under the following terms:

  • Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.

  • NonCommercial — You may not use the material for commercial purposes.