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Affinity Depletion of Plasma and Serum for Mass Spectrometry-Based Proteome Analysis

  • Julian A. J. Jaros
  • Paul C. Guest
  • Sabine Bahn
  • Daniel Martins-de-Souza
Part of the Methods in Molecular Biology book series (MIMB, volume 1002)

Abstract

Protein biomarker discovery in blood plasma and serum is severely hampered by the vast dynamic range of the proteome. With protein concentrations spanning 12 orders of magnitude, conventional mass spectrometric analysis allows for detection of only a few low-abundance proteins. Prior depletion of high-abundant proteins from the sample can increase analytical depth considerably and has become a widely used practice. We describe in detail an affinity depletion method that selectively removes 14 of the most abundant proteins in plasma and serum.

Key words

Plasma Serum Depletion High abundant Analytical depth Removal Biomarker Mass spectrometry CSF Cerebrospinal fluid Agilent Sigma 

Notes

Acknowledgments

This work was supported by the Stanley Medical Research Institute (SMRI, USA), Psynova Neurotech (UK), and European Union FP7 SchizDX research program (grant reference 223427).

JAJJ and DMS declare no conflict of interest. PCG and SB are consultants for Myriad-RBM although this does interfere with Springer Science policies with regards to sharing of data or materials.

References

  1. 1.
    Zhou M, Lucas DA, Chan KC et al (2004) An investigation into the human serum “interactome”. Electrophoresis 25:1289–1298PubMedCrossRefGoogle Scholar
  2. 2.
    Rai AJ, Gelfand CA, Haywood BC et al (2005) HUPO Plasma Proteome Project specimen collection and handling: towards the standardization of parameters for plasma proteome samples. Proteomics 5:3262–3277PubMedCrossRefGoogle Scholar
  3. 3.
    Burtis CA, Ashwood ER (2001) Tietz fundamentals of clinical chemistry, 5th edn. Saunders Company, Philadelphia, PAGoogle Scholar
  4. 4.
    Wrotnowski C (1998) The future of plasma proteins. Gen Eng News 18:14Google Scholar
  5. 5.
    Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1:845–867PubMedCrossRefGoogle Scholar
  6. 6.
    Tirumalai RS, Chan KC, Prieto DA, Issaq HJ, Conrads TP, Veenstra TD (2003) Characterization of the low molecular weight human serum proteome. Mol Cell Proteomics 2:1096–1103PubMedCrossRefGoogle Scholar
  7. 7.
    Hoffman SA, Joo WA, Echan LA, Speicher DW (2007) Higher dimensional (Hi-D) separation strategies dramatically improve the potential for cancer biomarker detection in serum and plasma. J Chromatogr B Analyt Technol Biomed Life Sci 849:43–52PubMedCrossRefGoogle Scholar
  8. 8.
    Annesley TM (2003) Ion suppression in mass spectrometry. Clin Chem 49:1041–1044PubMedCrossRefGoogle Scholar
  9. 9.
    Faca V, Pitteri SJ, Newcomb L et al (2007) Contribution of protein fractionation to depth of analysis of the serum and plasma proteomes. J Proteome Res 6:3558–3565PubMedCrossRefGoogle Scholar
  10. 10.
    Smith MPW, Wood SL, Zougman A et al (2011) A systematic analysis of the effects of increasing degrees of serum immunodepletion in terms of depth of coverage and other key aspects in top-down and bottom-up proteomic analyses. Proteomics 11:2222–2235PubMedCrossRefGoogle Scholar
  11. 11.
    Tang H-Y, Beer LA, Barnhart KT, Speicher DW (2011) Rapid verification of candidate serological biomarkers using gel-based, label-free multiple reaction monitoring. J Proteome Res 10:4005–4017PubMedCrossRefGoogle Scholar
  12. 12.
    Zhao L, Liu Y, Sun X, Peng K, Ding Y (2011) Serum proteome analysis for profiling protein markers associated with lymph node metastasis in colorectal carcinoma. J Comp Pathol 144:187–194PubMedCrossRefGoogle Scholar
  13. 13.
    Liao Q, Zhao L, Chen X, Deng Y, Ding Y (2008) Serum proteome analysis for profiling protein markers associated with carcinogenesis and lymph node metastasis in nasopharyngeal carcinoma. Clin Exp Metastasis 25:465–476PubMedCrossRefGoogle Scholar
  14. 14.
    Hamrita B, Chahed K, Trimeche M et al (2009) Proteomics-based identification of alpha1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas. Clin Chim Acta 404: 111–118PubMedCrossRefGoogle Scholar
  15. 15.
    Kaur P, Reis MD, Couchman GR, Forjuoh SN, Greene JF, Asea A (2010) SERPINE 1 links obesity and diabetes: a pilot study. J Proteomics Bioinform 3:191–199PubMedCrossRefGoogle Scholar
  16. 16.
    Fratantoni SA, Piersma SR, Jimenez CR (2010) Comparison of the performance of two affinity depletion spin filters for quantitative proteomics of CSF: evaluation of sensitivity and reproducibility of CSF analysis using GeLC-MS/MS and spectral counting. Proteomics Clin Appl 4:613–617PubMedCrossRefGoogle Scholar
  17. 17.
    Siegmund R, Kiehntopf M, Deufel T (2009) Evaluation of two different albumin depletion strategies for improved analysis of human CSF by SELDI-TOF-MS. Clin Biochem 42:1136–1143PubMedCrossRefGoogle Scholar
  18. 18.
    Zuberovic A, Hanrieder J, Hellman U, Bergquist J, Wetterhall M (2008) Proteome profiling of human cerebrospinal fluid: exploring the potential of capillary electrophoresis with surface modified capillaries for analysis of complex biological samples. Eur J Mass Spectrom 14:249–260CrossRefGoogle Scholar
  19. 19.
    Thouvenot E, Urbach S, Dantec C et al (2008) Enhanced detection of CNS cell secretome in plasma protein-depleted cerebrospinal fluid. J Proteome Res 7:4409–4421PubMedCrossRefGoogle Scholar
  20. 20.
    Sigdel TK, Lau K, Schilling J, Sarwal M (2008) Optimizing protein recovery for urinary proteomics, a tool to monitor renal transplantation. Clin Transplant 22:617–623PubMedCrossRefGoogle Scholar
  21. 21.
    Zolotarjova N, Martosella J, Nicol G, Bailey J, Boyes BE, Barrett WC (2005) Differences among techniques for high-abundant protein depletion. Proteomics 5:3304–3313PubMedCrossRefGoogle Scholar
  22. 22.
    Koutroukides TA, Guest PC, Leweke FM et al (2011) Characterization of the human serum depletome by label-free shotgun proteomics. J Sep Sci 34:1621–1626PubMedCrossRefGoogle Scholar
  23. 23.
    Fania C, Vasso M, Torretta E et al (2011) Setup for human sera MALDI profiling: the case of rhEPO treatment. Electrophoresis 32:1715–1727PubMedCrossRefGoogle Scholar
  24. 24.
    Martosella J, Zolotarjova N, Liu H, Nicol G, Boyes BE (2005) Reversed-phase high-performance liquid chromatographic prefractionation of immunodepleted human serum proteins to enhance mass spectrometry identification of lower-abundant proteins. J Proteome Res 4:1522–1537PubMedCrossRefGoogle Scholar
  25. 25.
    Björhall K, Miliotis T, Davidsson P (2005) Comparison of different depletion strategies for improved resolution in proteomic analysis of human serum samples. Proteomics 5:307–317PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Julian A. J. Jaros
    • 1
  • Paul C. Guest
    • 1
  • Sabine Bahn
    • 1
  • Daniel Martins-de-Souza
    • 2
    • 3
  1. 1.University of CambridgeCambridgeUK
  2. 2.Department of Chemical Engineering and BiotechnologyUniversity of CambridgeCambridgeUK
  3. 3.Lab. de Neurociencias (LIM-27), Inst. de Psiquaitria, Faculdade de Medicina da Universidade de Sao PauloSao PauloBrazil

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