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Multi-lectin Affinity Chromatography (M-LAC) Combined with Abundant Protein Depletion for Analysis of Human Plasma in Clinical Proteomics Applications

  • Marina HincapieEmail author
  • Tatiana Plavina
  • William S. Hancock
Chapter

Abstract

In this chapter we describe a robust sample preparation method for proteomic analysis of human plasma and discovery of candidate protein biomarkers. The method consists of depletion of the most abundant plasma proteins and multi-lectin affinity chromatography (M-LAC) to fractionate plasma into flow-through (unbound) and bound fractions, followed by nano-LC-MS/MS analysis of the digested proteins and label-free comparative quantitation. The performance of the method is monitored by several quality control checkpoints to assure reproducibility of the proteomic analysis. This approach reduces the complexity of plasma samples and significantly improves the overall dynamic range of protein detection, enabling detection of tissue leakage proteins present in plasma in ng/mL concentrations. In addition, the lectin-based fractionation of depleted plasma targets the plasma glycoproteome, permitting the identification of glycoproteins with disease-related differences in glycoform populations. The proteomics workflow was applied to the analysis of plasma from diseased patients affected with psoriasis and healthy donors. As an example of the effectiveness of the method we will present data from this biomarker study.

Keywords

Clinical proteomics Glycoproteins Lectin affinity chromatography Biomarker discovery Sample preparation 

Notes

Acknowledgements

This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) grants RO1 CA122591 and U01-CA128427 and by the Korean Research WCU grant R31-2008-000-10086-0. W. S. H and M .H. disclose that they have a financial interest in current efforts by Northeastern University and PeptiFarma to licence the M-LAC technology for biomarker discovery. Contribution Number 960 from the Barnett Institute.

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Marina Hincapie
    • 1
    Email author
  • Tatiana Plavina
    • 2
  • William S. Hancock
    • 1
  1. 1.The Barnett Institute of Chemical and Biological SciencesNortheastern UniversityBostonUSA
  2. 2.Biogen Idec, Inc.BostonUSA

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