Skip to main content
SpringerLink
Log in

Overview of Quantitative LC-MS Techniques for Proteomics and Activitomics

  • Protocol
  • First Online:
LC-MS/MS in Proteomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 658))

Abstract

LC-MS is a useful technique for protein and peptide quantification. In addition, as a powerful tool for systems biology research, LC-MS can also be used to quantify post-translational modifications and metabolites that reflect biochemical pathway activity. This review discusses the different analytical techniques that use LC-MS for the quantification of proteins, their modifications and activities in a multiplex manner.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Ross, P. L., Huang, Y. N., Marchese, J. N., Williamson, B., Parker, K., Hattan, S., Khainovski, N., Pillai, S., Dey, S., Daniels, S., Purkayastha, S., Juhasz, P., Martin, S., Bartlet-Jones, M., He, F., Jacobson, A., and Pappin, D. J. (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol. Cell. Proteomics 3, 1154–1169.

    Article  PubMed  CAS  Google Scholar 

  2. Gygi, S. P., Rist, B., Gerber, S. A., Turecek, F., Gelb, M. H., and Aebersold, R. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 17, 994–999.

    Article  PubMed  CAS  Google Scholar 

  3. Yao, X., Freas, A., Ramirez, J., Demirev, P. A., and Fenselau, C. (2001) Proteolytic 18O labeling for comparative proteomics: model studies with two serotypes of adenovirus. Anal. Chem. 73, 2836–2842.

    Article  PubMed  CAS  Google Scholar 

  4. Ong, S. E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., and Mann, M. (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol. Cell. Proteomics 1, 376–386.

    Article  PubMed  CAS  Google Scholar 

  5. Mueller, L. N., Brusniak, M. Y., Mani, D. R., and Aebersold, R. (2008) An assessment of software solutions for the analysis of mass spectrometry based quantitative proteomics data. J. Proteome Res. 7, 51–61.

    Article  PubMed  CAS  Google Scholar 

  6. Zeng, D., and Li, S. (2009) Improved CILAT reagents for quantitative proteomics. Bioorg. Med Chem Lett 19, 2059–2061.

    Article  PubMed  CAS  Google Scholar 

  7. Han, D. K., Eng, J., Zhou, H., and Aebersold, R. (2001) Quantitative profiling of differentiation-induced microsomal proteins using isotope-coded affinity tags and mass spectrometry. Nat. Biotechnol. 19, 946–951.

    Article  PubMed  CAS  Google Scholar 

  8. Griffin, T. J., Gygi, S. P., Rist, B., Aebersold, R., Loboda, A., Jilkine, A., Ens, W., and Standing, K. G. (2001) Quantitative proteomic analysis using a MALDI quadrupole time-of-flight mass spectrometer. Anal. Chem. 73, 978–986.

    Article  PubMed  CAS  Google Scholar 

  9. Zhang, R., Sioma, C. S., Thompson, R. A., Xiong, L., and Regnier, F. E. (2002) Controlling deuterium isotope effects in comparative proteomics. Anal. Chem. 74, 3662–3669.

    Article  PubMed  CAS  Google Scholar 

  10. Zhang, R., Sioma, C. S., Wang, S., and Regnier, F. E. (2001) Fractionation of isotopically labeled peptides in quantitative proteomics. Anal. Chem. 73, 5142–5149.

    Article  PubMed  CAS  Google Scholar 

  11. Borisov, O. V., Goshe, M. B., Conrads, T. P., Rakov, V. S., Veenstra, T. D., and Smith, R. D. (2002) Low-energy collision-induced dissociation fragmentation analysis of cysteinyl-modified peptides. Anal. Chem. 74, 2284–2292.

    Article  PubMed  CAS  Google Scholar 

  12. Yu, L. R., Conrads, T. P., Uo, T., Issaq, H. J., Morrison, R. S., and Veenstra, T. D. (2004) Evaluation of the acid-cleavable isotope-coded affinity tag reagents: application to camptothecin-treated cortical neurons. J. Proteome Res. 3, 469–477.

    Article  PubMed  CAS  Google Scholar 

  13. Molloy, M. P., Donohoe, S., Brzezinski, E. E., Kilby, G. W., Stevenson, T. I., Baker, J. D., Goodlett, D. R., and Gage, D. A. (2005) Large-scale evaluation of quantitative reproducibility and proteome coverage using acid cleavable isotope coded affinity tag mass spectrometry for proteomic profiling. Proteomics 5, 1204–1208.

    Article  PubMed  CAS  Google Scholar 

  14. Vaughn, C. P., Crockett, D. K., Lim, M. S., and Elenitoba-Johnson, K. S. (2006) Analytical characteristics of cleavable isotope-coded affinity tag-LC-tandem mass spectrometry for quantitative proteomic studies. J. Mol. Diagn. 8, 513–520.

    Article  PubMed  CAS  Google Scholar 

  15. Shiio, Y., and Aebersold, R. (2006) Quantitative proteome analysis using isotope-coded affinity tags and mass spectrometry. Nat. Protoc 1, 139–145.

    Article  PubMed  CAS  Google Scholar 

  16. Haqqani, A. S., Kelly, J. F., and Stanimirovic, D. B. (2008) Quantitative protein profiling by mass spectrometry using isotope-coded affinity tags. Methods Mol. Biol. 439, 225–240.

    Article  PubMed  CAS  Google Scholar 

  17. Pan, S., and Aebersold, R. (2007) Quantitative proteomics by stable isotope labeling and mass spectrometry. Methods Mol. Biol. 367, 209–218.

    PubMed  CAS  Google Scholar 

  18. Rivera-Monroy, Z., Bonn, G. K., and Guttman, A. (2009) Fluorescent isotopecoded affinity tag 2: peptide labeling and affinity capture. Electrophoresis 30, 1111–1118.

    Google Scholar 

  19. Bottari, P., Aebersold, R., Turecek, F., and Gelb, M. H. (2004) Design and synthesis of visible isotope-coded affinity tags for the absolute quantification of specific proteins in complex mixtures. Bioconjug. Chem. 15, 380–388.

    Article  PubMed  CAS  Google Scholar 

  20. Lu, Y., Bottari, P., Aebersold, R., Turecek, F., and Gelb, M. H. (2007) Absolute quantification of specific proteins in complex mixtures using visible isotope-coded affinity tags. Methods Mol. Biol. 359, 159–176.

    Article  PubMed  CAS  Google Scholar 

  21. Qiu, Y., Sousa, E. A., Hewick, R. M., and Wang, J. H. (2002) Acid-labile isotope-coded extractants: a class of reagents for quantitative mass spectrometric analysis of complex protein mixtures. Anal. Chem. 74, 4969–4979.

    Article  PubMed  CAS  Google Scholar 

  22. Whetstone, P. A., Butlin, N. G., Corneillie, T. M., and Meares, C. F. (2004) Element-coded affinity tags for peptides and proteins. Bioconjug. Chem. 15, 3–6.

    Article  PubMed  CAS  Google Scholar 

  23. Ahrends, R., Pieper, S., Neumann, B., Scheler, C., and Linscheid, M. W. (2009) Metal-coded affinity tag labeling: a demonstration of analytical robustness and suitability for biological applications. Anal. Chem. 81, 2176–2184.

    Article  PubMed  CAS  Google Scholar 

  24. Goshe, M. B., Conrads, T. P., Panisko, E. A., Angell, N. H., Veenstra, T. D., and Smith, R. D. (2001) Phosphoprotein isotope-coded affinity tag approach for isolating and quantitating phosphopeptides in proteome-wide analyses. Anal. Chem. 73, 2578–2586.

    Article  PubMed  CAS  Google Scholar 

  25. Qian, W. J., Goshe, M. B., Camp, D. G., 2nd, Yu, L. R., Tang, K., and Smith, R. D. (2003) Phosphoprotein isotope-coded solid-phase tag approach for enrichment and quantitative analysis of phosphopeptides from complex mixtures. Anal. Chem. 75, 5441–5450.

    Article  PubMed  CAS  Google Scholar 

  26. Vosseller, K., Hansen, K. C., Chalkley, R. J., Trinidad, J. C., Wells, L., Hart, G. W., and Burlingame, A. L. (2005) Quantitative analysis of both protein expression and serine/threonine post-translational modifications through stable isotope labeling with dithiothreitol. Proteomics 5, 388–398.

    Article  PubMed  CAS  Google Scholar 

  27. Sethuraman, M., McComb, M. E., Heibeck, T., Costello, C. E., and Cohen, R. A. (2004) Isotope-coded affinity tag approach to identify and quantify oxidant-sensitive protein thiols. Mol. Cell. Proteomics 3, 273–278. Epub 2004 Jan 2015.

    Article  PubMed  CAS  Google Scholar 

  28. Hagglund, P., Bunkenborg, J., Maeda, K., and Svensson, B. (2008) Identification of thioredoxin disulfide targets using a quantitative proteomics approach based on isotope-coded affinity tags. J. Proteome Res. 7, 5270–5276.

    Google Scholar 

  29. Hsu, J. L., Huang, S. Y., Chow, N. H., and Chen, S. H. (2003) Stable-isotope dimethyl labeling for quantitative proteomics. Anal. Chem. 75, 6843–6852.

    Article  PubMed  CAS  Google Scholar 

  30. Boersema, P. J., Raijmakers, R., Lemeer, S., Mohammed, S., and Heck, A. J. (2009) Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics. Nat. Protoc 4, 484–494.

    Article  PubMed  CAS  Google Scholar 

  31. Lemmel, C., Weik, S., Eberle, U., Dengjel, J., Kratt, T., Becker, H. D., Rammensee, H. G., and Stevanovic, S. (2004) Differential quantitative analysis of MHC ligands by mass spectrometry using stable isotope labeling. Nat. Biotechnol. 22, 450–454.

    Article  PubMed  CAS  Google Scholar 

  32. Zappacosta, F., and Annan, R. S. (2004) N-terminal isotope tagging strategy for quantitative proteomics: results-driven analysis of protein abundance changes. Anal. Chem. 76, 6618–6627.

    Article  PubMed  CAS  Google Scholar 

  33. Huang, H., Hittle, J., Zappacosta, F., Annan, R. S., Hershko, A., and Yen, T. J. (2008) Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit. J. Cell Biol. 183, 667–680.

    Article  PubMed  CAS  Google Scholar 

  34. Che, F. Y., and Fricker, L. D. (2005) Quantitative peptidomics of mouse pituitary: comparison of different stable isotopic tags. J. Mass Spectrom. 40, 238–249.

    Article  PubMed  CAS  Google Scholar 

  35. Ji, J., Chakraborty, A., Geng, M., Zhang, X., Amini, A., Bina, M., and Regnier, F. (2000) Strategy for qualitative and quantitative analysis in proteomics based on signature peptides. J. Chromatogr. 745, 197–210.

    Article  CAS  Google Scholar 

  36. Chakraborty, A., and Regnier, F. E. (2002) Global internal standard technology for comparative proteomics. J. Chromatogr. A 949, 173–184.

    Article  PubMed  CAS  Google Scholar 

  37. Mason, D. E., and Liebler, D. C. (2003) Quantitative analysis of modified proteins by LC-MS/MS of peptides labeled with phenyl isocyanate. J. Proteome Res. 2, 265–272.

    Article  PubMed  CAS  Google Scholar 

  38. Munchbach, M., Quadroni, M., Miotto, G., and James, P. (2000) Quantitation and facilitated de novo sequencing of proteins by isotopic N-terminal labeling of peptides with a fragmentation-directing moiety. Anal. Chem. 72, 4047–4057.

    Article  PubMed  CAS  Google Scholar 

  39. Goodlett, D. R., Keller, A., Watts, J. D., Newitt, R., Yi, E. C., Purvine, S., Eng, J. K., von Haller, P., Aebersold, R., and Kolker, E. (2001) Differential stable isotope labeling of peptides for quantitation and de novo sequence derivation. Rapid Commun. Mass Spectrom. 15, 1214–1221.

    Article  PubMed  CAS  Google Scholar 

  40. Zhang, R., and Regnier, F. E. (2002) Minimizing resolution of isotopically coded peptides in comparative proteomics. J. Proteome Res. 1, 139–147.

    Article  PubMed  CAS  Google Scholar 

  41. Morano, C., Zhang, X., and Fricker, L. D. (2008) Multiple isotopic labels for quantitative mass spectrometry. Anal. Chem. 80, 9298–9309.

    Google Scholar 

  42. Schmidt, A., Bisle, B., and Kislinger, T. (2009) Quantitative peptide and protein profiling by mass spectrometry. Methods Mol. Biol. 492, 21–38.

    Article  PubMed  CAS  Google Scholar 

  43. Mirgorodskaya, O. A., Kozmin, Y. P., Titov, M. I., Korner, R., Sonksen, C. P., and Roepstorff, P. (2000) Quantitation of peptides and proteins by matrix-assisted laser desorption/ionization mass spectrometry using (18)O-labeled internal standards. Rapid Commun. Mass Spectrom. 14, 1226–1232.

    Article  PubMed  CAS  Google Scholar 

  44. Stewart, II, Thomson, T., and Figeys, D. (2001) 18O labeling: a tool for proteomics. Rapid Commun. Mass Spectrom. 15, 2456–2465.

    Article  PubMed  CAS  Google Scholar 

  45. Reynolds, K. J., Yao, X., and Fenselau, C. (2002) Proteolytic 18O labeling for comparative proteomics: evaluation of endoprotease Glu-C as the catalytic agent. J. Proteome Res. 1, 27–33.

    Article  PubMed  CAS  Google Scholar 

  46. Qian, W. J., Monroe, M. E., Liu, T., Jacobs, J. M., Anderson, G. A., Shen, Y., Moore, R. J., Anderson, D. J., Zhang, R., Calvano, S. E., Lowry, S. F., Xiao, W., Moldawer, L. L., Davis, R. W., Tompkins, R. G., Camp, D. G., 2nd, and Smith, R. D. (2005) Quantitative proteome analysis of human plasma following in vivo lipopolysaccharide administration using 16O/18O labeling and the accurate mass and time tag approach. Mol. Cell. Proteomics 4, 700–709.

    Article  PubMed  CAS  Google Scholar 

  47. Ding, S. J., Wang, Y., Jacobs, J. M., Qian, W. J., Yang, F., Tolmachev, A. V., Du, X., Wang, W., Moore, R. J., Monroe, M. E., Purvine, S. O., Waters, K., Heibeck, T. H., Adkins, J. N., Camp, D. G., 2nd, Klemke, R. L., and Smith, R. D. (2008) Quantitative phosphoproteome analysis of lysophosphatidic acid induced chemotaxis applying dual-step (18)O labeling coupled with immobilized metal-ion affinity chromatography. J. Proteome Res. 7, 4215–4224.

    Article  PubMed  CAS  Google Scholar 

  48. Bantscheff, M., Dumpelfeld, B., and Kuster, B. (2004) Femtomol sensitivity post-digest (18)O labeling for relative quantification of differential protein complex composition. Rapid Commun. Mass Spectrom. 18, 869–876.

    Article  PubMed  CAS  Google Scholar 

  49. Qian, W. J., Liu, T., Petyuk, V. A., Gritsenko, M. A., Petritis, B. O., Polpitiya, A. D., Kaushal, A., Xiao, W., Finnerty, C. C., Jeschke, M. G., Jaitly, N., Monroe, M. E., Moore, R. J., Moldawer, L. L., Davis, R. W., Tompkins, R. G., Herndon, D. N., Camp, D. G., and Smith, R. D. (2009) Large-scale multiplexed quantitative discovery proteomics enabled by the use of an (18)O-labeled "universal" reference sample. J. Proteome Res. 8, 290–299.

    Article  PubMed  CAS  Google Scholar 

  50. Julka, S., and Regnier, F. (2004) Quantification in proteomics through stable isotope coding: a review. J. Proteome Res. 3, 350–363.

    Article  PubMed  CAS  Google Scholar 

  51. Johnson, K. L., and Muddiman, D. C. (2004) A method for calculating 16O/18O peptide ion ratios for the relative quantification of proteomes. J. Am. Soc. Mass Spectrom. 15, 437–445.

    Article  PubMed  CAS  Google Scholar 

  52. Rao, K. C., Carruth, R. T., and Miyagi, M. (2005) Proteolytic 18O labeling by peptidyl-Lys metalloendopeptidase for comparative proteomics. J. Proteome Res. 4, 507–514.

    Article  PubMed  CAS  Google Scholar 

  53. Choe, L., D’Ascenzo, M., Relkin, N. R., Pappin, D., Ross, P., Williamson, B., Guertin, S., Pribil, P., and Lee, K. H. (2007) 8-plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer’s disease. Proteomics 7, 3651–3660.

    Article  PubMed  CAS  Google Scholar 

  54. Pierce, A., Unwin, R. D., Evans, C. A., Griffiths, S., Carney, L., Zhang, L., Jaworska, E., Lee, C. F., Blinco, D., Okoniewski, M. J., Miller, C. J., Bitton, D. A., Spooncer, E., and Whetton, A. D. (2008) Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. Mol. Cell. Proteomics 7, 853–863.

    Article  PubMed  CAS  Google Scholar 

  55. Phanstiel, D., Unwin, R., McAlister, G. C., and Coon, J. J. (2009) Peptide quantification using 8-plex isobaric tags and electron transfer dissociation tandem mass spectrometry. Anal. Chem. 81, 1693–1698.

    Article  PubMed  CAS  Google Scholar 

  56. Unwin, R. D., Pierce, A., Watson, R. B., Sternberg, D. W., and Whetton, A. D. (2005) Quantitative proteomic analysis using isobaric protein tags enables rapid comparison of changes in transcript and protein levels in transformed cells. Mol. Cell. Proteomics 22, 22.

    Google Scholar 

  57. Pflieger, D., Junger, M. A., Muller, M., Rinner, O., Lee, H., Gehrig, P. M., Gstaiger, M., and Aebersold, R. (2008) Quantitative proteomic analysis of protein complexes: concurrent identification of interactors and their state of phosphorylation. Mol. Cell. Proteomics 7, 326–346.

    PubMed  CAS  Google Scholar 

  58. Butler, G. S., Dean, R. A., Smith, D., and Overall, C. M. (2009) Membrane protease degradomics: proteomic identification and quantification of cell surface protease substrates. Methods Mol. Biol. 528, 159–176.

    Article  PubMed  CAS  Google Scholar 

  59. Chen, Y., Choong, L. Y., Lin, Q., Philp, R., Wong, C. H., Ang, B. K., Tan, Y. L., Loh, M. C., Hew, C. L., Shah, N., Druker, B. J., Chong, P. K., and Lim, Y. P. (2007) Differential expression of novel tyrosine kinase substrates during breast cancer development. Mol. Cell. Proteomics 6, 2072–2087.

    Article  PubMed  CAS  Google Scholar 

  60. Chiappetta, G., Corbo, C., Palmese, A., Marino, G., and Amoresano, A. (2009) Quantitative identification of protein nitration sites. Proteomics 9, 1524–1537.

    Article  PubMed  CAS  Google Scholar 

  61. Dean, R. A., and Overall, C. M. (2007) Proteomics discovery of metalloproteinase substrates in the cellular context by iTRAQ labeling reveals a diverse MMP-2 substrate degradome. Mol. Cell. Proteomics 6, 611–623.

    Article  PubMed  CAS  Google Scholar 

  62. Enoksson, M., Li, J., Ivancic, M. M., Timmer, J. C., Wildfang, E., Eroshkin, A., Salvesen, G. S., and Tao, W. A. (2007) Identification of proteolytic cleavage sites by quantitative proteomics. J. Proteome Res. 6, 2850–2858.

    Article  PubMed  CAS  Google Scholar 

  63. Meany, D. L., Xie, H., Thompson, L. V., Arriaga, E. A., and Griffin, T. J. (2007) Identification of carbonylated proteins from enriched rat skeletal muscle mitochondria using affinity chromatography-stable isotope labeling and tandem mass spectrometry. Proteomics 7, 1150–1163.

    Article  PubMed  CAS  Google Scholar 

  64. Wang, X., and Huang, L. (2008) Identifying dynamic interactors of protein complexes by quantitative mass spectrometry. Mol. Cell. Proteomics 7, 46–57.

    PubMed  Google Scholar 

  65. Zhang, Y., Wolf-Yadlin, A., Ross, P. L., Pappin, D. J., Rush, J., Lauffenburger, D. A., and White, F. M. (2005) Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Mol. Cell. Proteomics 4, 1240–1250.

    Article  PubMed  CAS  Google Scholar 

  66. Keshamouni, V. G., Jagtap, P., Michailidis, G., Strahler, J. R., Kuick, R., Reka, A. K., Papoulias, P., Krishnapuram, R., Srirangam, A., Standiford, T. J., Andrews, P. C., and Omenn, G. S. (2009) Temporal quantitative proteomics by iTRAQ 2D-LC-MS/MS and corresponding mRNA expression analysis identify post-transcriptional modulation of actin-cytoskeleton regulators during TGF-beta-induced epithelial–mesenchymal transition. J. Proteome Res. 8, 35–47.

    Article  PubMed  CAS  Google Scholar 

  67. Yan, W., Hwang, D., and Aebersold, R. (2008) Quantitative proteomic analysis to profile dynamic changes in the spatial distribution of cellular proteins. Methods Mol. Biol. 432, 389–401.

    Article  PubMed  CAS  Google Scholar 

  68. Chen, X., and Andrews, P. C. (2008) Purification and proteomics analysis of pancreatic zymogen granule membranes. Methods Mol. Biol. 432, 275–287.

    Article  PubMed  CAS  Google Scholar 

  69. Dwivedi, R. C., Dhindsa, N., Krokhin, O. V., Cortens, J., Wilkins, J. A., and El-Gabalawy, H. S. (2009) The effects of infliximab therapy on the serum proteome of rheumatoid arthritis patients. Arthritis Res. Ther. 11, R32.

    Article  PubMed  CAS  Google Scholar 

  70. Bantscheff, M., Boesche, M., Eberhard, D., Matthieson, T., Sweetman, G., and Kuster, B. (2008) Robust and sensitive iTRAQ quantification on an LTQ Orbitrap mass spectrometer. Mol. Cell. Proteomics 7, 1702–1713.

    Article  PubMed  CAS  Google Scholar 

  71. Ralhan, R., Desouza, L. V., Matta, A., Chandra Tripathi, S., Ghanny, S., Dattagupta, S., Thakar, A., Chauhan, S. S., and Siu, K. W. (2009) iTRAQ-multidimensional liquid chromatography and tandem mass spectrometry-based identification of potential biomarkers of oral epithelial dysplasia and novel networks between inflammation and premalignancy. J. Proteome Res. 8, 300–309.

    Article  PubMed  CAS  Google Scholar 

  72. Ho, J., Kong, J. W., Choong, L. Y., Loh, M. C., Toy, W., Chong, P. K., Wong, C. H., Wong, C. Y., Shah, N., and Lim, Y. P. (2009) Novel breast cancer metastasis-associated proteins. J. Proteome Res. 8, 583–594.

    Article  PubMed  CAS  Google Scholar 

  73. Quaglia, M., Pritchard, C., Hall, Z., and O’Connor, G. (2008) Amine-reactive isobaric tagging reagents: requirements for absolute quantification of proteins and peptides. Anal. Biochem. 379, 164–169.

    Article  PubMed  CAS  Google Scholar 

  74. Thompson, A., Schafer, J., Kuhn, K., Kienle, S., Schwarz, J., Schmidt, G., Neumann, T., Johnstone, R., Mohammed, A. K., and Hamon, C. (2003) Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal. Chem. 75, 1895–1904.

    Article  PubMed  CAS  Google Scholar 

  75. Dayon, L., Hainard, A., Licker, V., Turck, N., Kuhn, K., Hochstrasser, D. F., Burkhard, P. R., and Sanchez, J. C. (2008) Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags. Anal. Chem. 80, 2921–2931.

    Article  PubMed  CAS  Google Scholar 

  76. Viner, R. I., Zhang, T., Second, T., and Zabrouskov, V. (2009) Quantification of post-translationally modified peptides of bovine alpha-crystallin using tandem mass tags and electron transfer dissociation. J. Proteomics 72, 874–885.

    Google Scholar 

  77. Li, S., and Zeng, D. (2007) CILAT―a new reagent for quantitative proteomics. Chem. Commun. (Cambridge, England), 2181–2183.

    Google Scholar 

  78. DeSouza, L. V., Taylor, A. M., Li, W., Minkoff, M. S., Romaschin, A. D., Colgan, T. J., and Siu, K. W. (2008) Multiple reaction monitoring of mTRAQ-labeled peptides enables absolute quantification of endogenous levels of a potential cancer marker in cancerous and normal endometrial tissues. J. Proteome Res. 7, 3525–3534.

    Article  PubMed  CAS  Google Scholar 

  79. Boehm, A. M., Putz, S., Altenhofer, D., Sickmann, A., and Falk, M. (2007) Precise protein quantification based on peptide quantification using iTRAQ. BMC Bioinformatics 8, 214.

    Article  PubMed  CAS  Google Scholar 

  80. D’Ascenzo, M., Choe, L., and Lee, K. H. (2008) iTRAQPak: an R based analysis and visualization package for 8-plex isobaric protein expression data. Brief Funct. Genomic Proteomic 7, 127–135.

    Article  PubMed  CAS  Google Scholar 

  81. Hundertmark, C., Fischer, R., Reinl, T., May, S., Klawonn, F., and Jansch, L. (2009) MS-specific noise model reveals the potential of iTRAQ in quantitative proteomics. Bioinformatics (Oxford, England) 25, 1004–1011.

    Article  CAS  Google Scholar 

  82. Lacerda, C. M., Xin, L., Rogers, I., and Reardon, K. F. (2008) Analysis of iTRAQ data using Mascot and peaks quantification algorithms. Brief Funct. Genomic Proteomic 7, 119–126.

    Article  PubMed  CAS  Google Scholar 

  83. Laderas, T., Bystrom, C., McMillen, D., Fan, G., and McWeeney, S. (2007) TandTRAQ: an open-source tool for integrated protein identification and quantitation. Bioinformatics (Oxford, England) 23, 3394–3396.

    Article  CAS  Google Scholar 

  84. Lin, W. T., Hung, W. N., Yian, Y. H., Wu, K. P., Han, C. L., Chen, Y. R., Chen, Y. J., Sung, T. Y., and Hsu, W. L. (2006) Multi-Q: a fully automated tool for multiplexed protein quantitation. J. Proteome Res. 5, 2328–2338.

    Article  PubMed  CAS  Google Scholar 

  85. Shadforth, I. P., Dunkley, T. P., Lilley, K. S., and Bessant, C. (2005) i-Tracker: for quantitative proteomics using iTRAQ. BMC Genomics 6, 145.

    Article  PubMed  CAS  Google Scholar 

  86. Yu, C. Y., Tsui, Y. H., Yian, Y. H., Sung, T. Y., and Hsu, W. L. (2007) The Multi-Q web server for multiplexed protein quantitation. Nucleic Acids Res. 35, W707–W712.

    Article  PubMed  Google Scholar 

  87. Hill, E. G., Schwacke, J. H., Comte-Walters, S., Slate, E. H., Oberg, A. L., Eckel-Passow, J. E., Therneau, T. M., and Schey, K. L. (2008) A statistical model for iTRAQ data analysis. J. Proteome Res. 7, 3091–3101.

    Article  PubMed  CAS  Google Scholar 

  88. Griffin, T. J., Xie, H., Bandhakavi, S., Popko, J., Mohan, A., Carlis, J. V., and Higgins, L. (2007) iTRAQ reagent-based quantitative proteomic analysis on a linear ion trap mass spectrometer. J. Proteome Res. 6, 4200–4209.

    Article  PubMed  CAS  Google Scholar 

  89. Guo, T., Gan, C. S., Zhang, H., Zhu, Y., Kon, O. L., and Sze, S. K. (2008) Hybridization of pulsed-Q dissociation and collision-activated dissociation in linear ion trap mass spectrometer for iTRAQ quantitation. J. Proteome Res. 7, 4831–4840.

    Article  PubMed  CAS  Google Scholar 

  90. Oda, Y., Huang, K., Cross, F. R., Cowburn, D., and Chait, B. T. (1999) Accurate quantitation of protein expression and site-specific phosphorylation. Proc. Natl. Acad. Sci. USA 96, 6591–6596.

    Article  PubMed  CAS  Google Scholar 

  91. Conrads, T. P., Alving, K., Veenstra, T. D., Belov, M. E., Anderson, G. A., Anderson, D. J., Lipton, M. S., Pasa-Tolic, L., Udseth, H. R., Chrisler, W. B., Thrall, B. D., and Smith, R. D. (2001) Quantitative analysis of bacterial and mammalian proteomes using a combination of cysteine affinity tags and 15N-metabolic labeling. Anal. Chem. 73, 2132–2139.

    Article  PubMed  CAS  Google Scholar 

  92. Washburn, M. P., Koller, A., Oshiro, G., Ulaszek, R. R., Plouffe, D., Deciu, C., Winzeler, E., and Yates, J. R., 3rd. (2003) Protein pathway and complex clustering of correlated mRNA and protein expression analyses in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 100, 3107–3112.

    Article  PubMed  CAS  Google Scholar 

  93. Bindschedler, L. V., Palmblad, M., and Cramer, R. (2008) Hydroponic isotope labelling of entire plants (HILEP) for quantitative plant proteomics; an oxidative stress case study. Phytochemistry 69, 1962–1972.

    Article  PubMed  CAS  Google Scholar 

  94. Pan, C., Gnad, F., Olsen, J. V., and Mann, M. (2008) Quantitative phosphoproteome analysis of a mouse liver cell line reveals specificity of phosphatase inhibitors. Proteomics 8, 4534–4546.

    Article  PubMed  CAS  Google Scholar 

  95. Molina, H., Parmigiani, G., and Pandey, A. (2005) Assessing reproducibility of a protein dynamics study using in vivo labeling and liquid chromatography tandem mass spectrometry. Anal. Chem. 77, 2739–2744.

    Article  PubMed  CAS  Google Scholar 

  96. Molina, H., Yang, Y., Ruch, T., Kim, J. W., Mortensen, P., Otto, T., Nalli, A., Tang, Q. Q., Lane, M. D., Chaerkady, R., and Pandey, A. (2009) Temporal profiling of the adipocyte proteome during differentiation using a five-plex SILAC based strategy. J. Proteome Res. 8, 48–58.

    Article  PubMed  CAS  Google Scholar 

  97. Harsha, H. C., Molina, H., and Pandey, A. (2008) Quantitative proteomics using stable isotope labeling with amino acids in cell culture. Nat. Protoc 3, 505–516.

    Article  PubMed  CAS  Google Scholar 

  98. Gruhler, S., and Kratchmarova, I. (2008) Stable isotope labeling by amino acids in cell culture (SILAC). Methods Mol. Biol. 424, 101–111.

    Article  PubMed  CAS  Google Scholar 

  99. Ong, S. E., and Mann, M. (2007) Stable isotope labeling by amino acids in cell culture for quantitative proteomics. Methods Mol. Biol. 359, 37–52.

    Article  PubMed  CAS  Google Scholar 

  100. Cox, J., Matic, I., Hilger, M., Nagaraj, N., Selbach, M., Olsen, J. V., and Mann, M. (2009) A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics. Nat. Protoc 4, 698–705.

    Article  PubMed  CAS  Google Scholar 

  101. Graumann, J., Hubner, N. C., Kim, J. B., Ko, K., Moser, M., Kumar, C., Cox, J., Scholer, H., and Mann, M. (2008) Stable isotope labeling by amino acids in cell culture (SILAC) and proteome quantitation of mouse embryonic stem cells to a depth of 5,111 proteins. Mol. Cell. Proteomics 7, 672–683.

    PubMed  CAS  Google Scholar 

  102. Schwanhausser, B., Gossen, M., Dittmar, G., and Selbach, M. (2009) Global analysis of cellular protein translation by pulsed SILAC. Proteomics 9, 205–209.

    Article  PubMed  CAS  Google Scholar 

  103. Doherty, M. K., Hammond, D. E., Clague, M. J., Gaskell, S. J., and Beynon, R. J. (2009) Turnover of the human proteome: determination of protein intracellular stability by dynamic SILAC. J. Proteome Res. 8, 104–112.

    Article  PubMed  CAS  Google Scholar 

  104. Mintz, M., Vanderver, A., Brown, K. J., Lin, J., Wang, Z., Kaneski, C., Schiffmann, R., Nagaraju, K., Hoffman, E. P., and Hathout, Y. (2008) Time series proteome profiling to study endoplasmic reticulum stress response. J. Proteome Res. 7, 2435–2444.

    Article  PubMed  CAS  Google Scholar 

  105. Wang, M., You, J., Bemis, K. G., Tegeler, T. J., and Brown, D. P. (2008) Label-free mass spectrometry-based protein quantification technologies in proteomic analysis. Brief Funct. Genomic Proteomic 7, 329–339.

    Article  PubMed  CAS  Google Scholar 

  106. Trinkle-Mulcahy, L., Boulon, S., Lam, Y. W., Urcia, R., Boisvert, F. M., Vandermoere, F., Morrice, N. A., Swift, S., Rothbauer, U., Leonhardt, H., and Lamond, A. (2008) Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes. J. Cell Biol. 183, 223–239.

    Article  PubMed  CAS  Google Scholar 

  107. Mousson, F., Kolkman, A., Pijnappel, W. W., Timmers, H. T., and Heck, A. J. (2008) Quantitative proteomics reveals regulation of dynamic components within TATA-binding protein (TBP) transcription complexes. Mol. Cell. Proteomics 7, 845–852.

    Article  PubMed  CAS  Google Scholar 

  108. Dobreva, I., Fielding, A., Foster, L. J., and Dedhar, S. (2008) Mapping the integrin-linked kinase interactome using SILAC. J. Proteome Res. 7, 1740–1749.

    Article  PubMed  CAS  Google Scholar 

  109. Guerrero, C., Tagwerker, C., Kaiser, P., and Huang, L. (2006) An integrated mass spectrometry-based proteomic approach: quantitative analysis of tandem affinity-purified in vivo cross-linked protein complexes (QTAX) to decipher the 26 S proteasome-interacting network. Mol. Cell. Proteomics 5, 366–378.

    PubMed  CAS  Google Scholar 

  110. Blagoev, B., Kratchmarova, I., Ong, S. E., Nielsen, M., Foster, L. J., and Mann, M. (2003) A proteomics strategy to elucidate functional protein–protein interactions applied to EGF signaling. Nat. Biotechnol. 21, 315–318.

    Article  PubMed  CAS  Google Scholar 

  111. Mittler, G., Butter, F., and Mann, M. (2009) A SILAC-based DNA protein interaction screen that identifies candidate binding proteins to functional DNA elements. Genome Res. 19, 284–293.

    Article  PubMed  CAS  Google Scholar 

  112. Ong, S. E., Schenone, M., Margolin, A. A., Li, X., Do, K., Doud, M. K., Mani, D. R., Kuai, L., Wang, X., Wood, J. L., Tolliday, N. J., Koehler, A. N., Marcaurelle, L. A., Golub, T. R., Gould, R. J., Schreiber, S. L., and Carr, S. A. (2009) Identifying the proteins to which small-molecule probes and drugs bind in cells. Proc. Natl. Acad. Sci. USA 106, 4617–4622.

    Article  PubMed  CAS  Google Scholar 

  113. Oppermann, F. S., Gnad, F., Olsen, J. V., Hornberger, R., Greff, Z., Keri, G., Mann, M., and Daub, H. (2009) Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics 8, 1751–1764.

    Google Scholar 

  114. Hanke, S., and Mann, M. (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. Mol. Cell. Proteomics 8, 519–534.

    Article  PubMed  CAS  Google Scholar 

  115. Yan, Y., Weaver, V. M., and Blair, I. A. (2005) Analysis of protein expression during oxidative stress in breast epithelial cells using a stable isotope labeled proteome internal standard. J. Proteome Res. 4, 2007–2014.

    Article  PubMed  CAS  Google Scholar 

  116. Hanke, S., Besir, H., Oesterhelt, D., and Mann, M. (2008) Absolute SILAC for accurate quantitation of proteins in complex mixtures down to the attomole level. J. Proteome Res. 7, 1118–1130.

    Article  PubMed  CAS  Google Scholar 

  117. Ong, S. E., Mittler, G., and Mann, M. (2004) Identifying and quantifying in vivo methylation sites by heavy methyl SILAC. Nat. Methods 1, 119–126.

    Article  PubMed  CAS  Google Scholar 

  118. Colzani, M., Schutz, F., Potts, A., Waridel, P., and Quadroni, M. (2008) Relative protein quantification by isobaric SILAC with immonium ion splitting (ISIS). Mol. Cell. Proteomics 7, 927–937.

    Article  PubMed  CAS  Google Scholar 

  119. Kruger, M., Moser, M., Ussar, S., Thievessen, I., Luber, C. A., Forner, F., Schmidt, S., Zanivan, S., Fassler, R., and Mann, M. (2008) SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell 134, 353–364.

    Article  PubMed  CAS  Google Scholar 

  120. Ong, S. E., Kratchmarova, I., and Mann, M. (2003) Properties of 13C-substituted arginine in stable isotope labeling by amino acids in cell culture (SILAC). J. Proteome Res. 2, 173–181.

    Article  PubMed  CAS  Google Scholar 

  121. Bendall, S. C., Hughes, C., Stewart, M. H., Doble, B., Bhatia, M., and Lajoie, G. A. (2008) Prevention of amino acid conversion in SILAC experiments with embryonic stem cells. Mol. Cell. Proteomics 7, 1587–1597.

    Article  PubMed  CAS  Google Scholar 

  122. Van Hoof, D., Pinkse, M. W., Oostwaard, D. W., Mummery, C. L., Heck, A. J., and Krijgsveld, J. (2007) An experimental correction for arginine-to-proline conversion artifacts in SILAC-based quantitative proteomics. Nat. Methods 4, 677–678.

    Article  PubMed  CAS  Google Scholar 

  123. America, A. H., and Cordewener, J. H. (2008) Comparative LC-MS: a landscape of peaks and valleys. Proteomics 8, 731–749.

    Article  PubMed  CAS  Google Scholar 

  124. Braisted, J. C., Kuntumalla, S., Vogel, C., Marcotte, E. M., Rodrigues, A. R., Wang, R., Huang, S. T., Ferlanti, E. S., Saeed, A. I., Fleischmann, R. D., Peterson, S. N., and Pieper, R. (2008) The APEX quantitative proteomics tool: generating protein quantitation estimates from LC-MS/MS proteomics results. BMC Bioinformatics 9, 529.

    Article  PubMed  CAS  Google Scholar 

  125. Cheng, F. Y., Blackburn, K., Lin, Y. M., Goshe, M. B., and Williamson, J. D. (2009) Absolute protein quantification by LC/MS(E) for global analysis of salicylic acid-induced plant protein secretion responses. J. Proteome Res. 8, 82–93.

    Article  PubMed  CAS  Google Scholar 

  126. Choi, H., Fermin, D., and Nesvizhskii, A. I. (2008) Significance analysis of spectral count data in label-free shotgun proteomics. Mol. Cell. Proteomics 7, 2373–2385.

    Article  PubMed  CAS  Google Scholar 

  127. Cutillas, P. R., Biber, J., Marks, J., Jacob, R., Stieger, B., Cramer, R., Waterfield, M., Burlingame, A. L., and Unwin, R. J. (2005) Proteomic analysis of plasma membrane vesicles isolated from the rat renal cortex. Proteomics 5, 101–112.

    Article  PubMed  CAS  Google Scholar 

  128. Cutillas, P. R., and Vanhaesebroeck, B. (2007) Quantitative profile of five murine core proteomes using label-free functional proteomics. Mol. Cell. Proteomics 6, 1560–1573.

    Article  PubMed  CAS  Google Scholar 

  129. Fang, R., Elias, D. A., Monroe, M. E., Shen, Y., McIntosh, M., Wang, P., Goddard, C. D., Callister, S. J., Moore, R. J., Gorby, Y. A., Adkins, J. N., Fredrickson, J. K., Lipton, M. S., and Smith, R. D. (2006) Differential label-free quantitative proteomic analysis of Shewanella oneidensis cultured under aerobic and suboxic conditions by accurate mass and time tag approach. Mol. Cell. Proteomics 5, 714–725.

    PubMed  CAS  Google Scholar 

  130. Fraterman, S., Zeiger, U., Khurana, T. S., Wilm, M., and Rubinstein, N. A. (2007) Quantitative proteomics profiling of sarcomere associated proteins in limb and extraocular muscle allotypes. Mol. Cell. Proteomics 6, 728–737.

    Article  PubMed  CAS  Google Scholar 

  131. Fu, X., Gharib, S. A., Green, P. S., Aitken, M. L., Frazer, D. A., Park, D. R., Vaisar, T., and Heinecke, J. W. (2008) Spectral index for assessment of differential protein expression in shotgun proteomics. J. Proteome Res. 7, 845–854.

    Article  PubMed  CAS  Google Scholar 

  132. Govorukhina, N., Horvatovich, P., and Bischoff, R. (2008) Label-free proteomics of serum. Methods Mol. Biol. 484, 67–77.

    Article  PubMed  CAS  Google Scholar 

  133. Haqqani, A. S., Kelly, J. F., and Stanimirovic, D. B. (2008) Quantitative protein profiling by mass spectrometry using label-free proteomics. Methods Mol. Biol. 439, 241–256.

    Article  PubMed  CAS  Google Scholar 

  134. Higgs, R. E., Knierman, M. D., Gelfanova, V., Butler, J. P., and Hale, J. E. (2005) Comprehensive label-free method for the relative quantification of proteins from biological samples. J. Proteome Res. 4, 1442–1450.

    Article  PubMed  CAS  Google Scholar 

  135. Higgs, R. E., Knierman, M. D., Gelfanova, V., Butler, J. P., and Hale, J. E. (2008) Label-free LC-MS method for the identification of biomarkers. Methods Mol. Biol. 428, 209–230.

    Article  PubMed  CAS  Google Scholar 

  136. Meng, F., Wiener, M. C., Sachs, J. R., Burns, C., Verma, P., Paweletz, C. P., Mazur, M. T., Deyanova, E. G., Yates, N. A., and Hendrickson, R. C. (2007) Quantitative analysis of complex peptide mixtures using FTMS and differential mass spectrometry. J. Am. Soc. Mass Spectrom. 18, 226–233.

    Article  PubMed  CAS  Google Scholar 

  137. Negishi, A., Ono, M., Handa, Y., Kato, H., Yamashita, K., Honda, K., Shitashige, M., Satow, R., Sakuma, T., Kuwabara, H., Omura, K., Hirohashi, S., and Yamada, T. (2009) Large-scale quantitative clinical proteomics by label-free liquid chromatography and mass spectrometry. Cancer Sci. 100, 514–519.

    Article  PubMed  CAS  Google Scholar 

  138. Ono, M., Shitashige, M., Honda, K., Isobe, T., Kuwabara, H., Matsuzuki, H., Hirohashi, S., and Yamada, T. (2006) Label-free quantitative proteomics using large peptide data sets generated by nanoflow liquid chromatography and mass spectrometry. Mol. Cell. Proteomics 5, 1338–1347.

    Article  PubMed  CAS  Google Scholar 

  139. Rinner, O., Mueller, L. N., Hubalek, M., Muller, M., Gstaiger, M., and Aebersold, R. (2007) An integrated mass spectrometric and computational framework for the analysis of protein interaction networks. Nat. Biotechnol. 25, 345–352.

    Article  PubMed  CAS  Google Scholar 

  140. Ru, Q. C., Zhu, L. A., Silberman, J., and Shriver, C. D. (2006) Label-free semiquantitative peptide feature profiling of human breast cancer and breast disease sera via two-dimensional liquid chromatography–mass spectrometry. Mol. Cell. Proteomics 5, 1095–1104.

    Article  PubMed  CAS  Google Scholar 

  141. Sardiu, M. E., Cai, Y., Jin, J., Swanson, S. K., Conaway, R. C., Conaway, J. W., Florens, L., and Washburn, M. P. (2008) Probabilistic assembly of human protein interaction networks from label-free quantitative proteomics. Proc. Natl. Acad. Sci. USA 105, 1454–1459.

    Article  PubMed  CAS  Google Scholar 

  142. Schmidt, M. W., Houseman, A., Ivanov, A. R., and Wolf, D. A. (2007) Comparative proteomic and transcriptomic profiling of the fission yeast Schizosaccharomyces pombe. Mol. Syst. Biol. 3, 79.

    Article  PubMed  CAS  Google Scholar 

  143. Silva, J. C., Denny, R., Dorschel, C., Gorenstein, M. V., Li, G. Z., Richardson, K., Wall, D., and Geromanos, S. J. (2006) Simultaneous qualitative and quantitative analysis of the Escherichia coli proteome: a sweet tale. Mol. Cell. Proteomics 5, 589–607.

    PubMed  CAS  Google Scholar 

  144. Tabata, T., Sato, T., Kuromitsu, J., and Oda, Y. (2007) Pseudo internal standard approach for label-free quantitative proteomics. Anal. Chem. 79, 8440–8445.

    Article  PubMed  CAS  Google Scholar 

  145. Wiener, M. C., Sachs, J. R., Deyanova, E. G., and Yates, N. A. (2004) Differential mass spectrometry: a label-free LC-MS method for finding significant differences in complex peptide and protein mixtures. Anal. Chem. 76, 6085–6096.

    Article  PubMed  CAS  Google Scholar 

  146. Mann, M. (1999) Quantitative proteomics? Nat. Biotechnol. 17, 954–955.

    Article  PubMed  CAS  Google Scholar 

  147. Gangl, E. T., Annan, M. M., Spooner, N., and Vouros, P. (2001) Reduction of signal suppression effects in ESI–MS using a nanosplitting device. Anal. Chem. 73, 5635–5644.

    Article  PubMed  CAS  Google Scholar 

  148. Shen, J. X., Motyka, R. J., Roach, J. P., and Hayes, R. N. (2005) Minimization of ion suppression in LC-MS/MS analysis through the application of strong cation exchange solid-phase extraction (SCX-SPE). J. Pharm. Biomed. Anal. 37, 359–367.

    Article  PubMed  CAS  Google Scholar 

  149. Weaver, R., and Riley, R. J. (2006) Identification and reduction of ion suppression effects on pharmacokinetic parameters by polyethylene glycol 400. Rapid Commun. Mass Spectrom. 20, 2559–2564.

    Article  PubMed  CAS  Google Scholar 

  150. Wilm, M., and Mann, M. (1994) Electrospray and Taylor-Cone theory, Dole's beam of macromolecules at last? Int. J. Mass Spectrom. Ion Process. 136, 167–180.

    Article  CAS  Google Scholar 

  151. Chelius, D., and Bondarenko, P. V. (2002) Quantitative profiling of proteins in complex mixtures using liquid chromatography and mass spectrometry. J. Proteome Res. 1, 317–323.

    Article  PubMed  CAS  Google Scholar 

  152. Cutillas, P. R., Geering, B., Waterfield, M. D., and Vanhaesebroeck, B. (2005) Quantification of gel-separated proteins and their phosphorylation sites by LC-MS using unlabeled internal standards: analysis of phosphoprotein dynamics in a B cell lymphoma cell line. Mol. Cell. Proteomics 4, 1038–1051.

    Article  PubMed  CAS  Google Scholar 

  153. Steen, H., Jebanathirajah, J. A., Springer, M., and Kirschner, M. W. (2005) Stable isotope-free relative and absolute quantitation of protein phosphorylation stoichiometry by MS. Proc. Natl. Acad. Sci. USA 102, 3948–3953.

    Article  PubMed  CAS  Google Scholar 

  154. America, A. H., Cordewener, J. H., van Geffen, M. H., Lommen, A., Vissers, J. P., Bino, R. J., and Hall, R. D. (2006) Alignment and statistical difference analysis of complex peptide data sets generated by multidimensional LC-MS. Proteomics 6, 641–653.

    Article  PubMed  CAS  Google Scholar 

  155. Zhang, B., VerBerkmoes, N. C., Langston, M. A., Uberbacher, E., Hettich, R. L., and Samatova, N. F. (2006) Detecting differential and correlated protein expression in label-free shotgun proteomics. J. Proteome Res. 5, 2909–2918.

    Article  PubMed  CAS  Google Scholar 

  156. Hixson, K. K. (2009) Label-free relative quantitation of prokaryotic proteomes using the accurate mass and time tag approach. Methods Mol. Biol. 492, 39–63.

    Article  PubMed  CAS  Google Scholar 

  157. Jaitly, N., Monroe, M. E., Petyuk, V. A., Clauss, T. R., Adkins, J. N., and Smith, R. D. (2006) Robust algorithm for alignment of liquid chromatography–mass spectrometry analyses in an accurate mass and time tag data analysis pipeline. Anal. Chem. 78, 7397–7409.

    Article  PubMed  CAS  Google Scholar 

  158. Luo, Q., Hixson, K. K., Callister, S. J., Lipton, M. S., Morris, B. E., and Krumholz, L. R. (2007) Proteome analysis of Desulfovibrio desulfuricans G20 mutants using the accurate mass and time (AMT) tag approach. J. Proteome Res. 6, 3042–3053.

    Article  PubMed  CAS  Google Scholar 

  159. Strittmatter, E. F., Ferguson, P. L., Tang, K., and Smith, R. D. (2003) Proteome analyses using accurate mass and elution time peptide tags with capillary LC time-of-flight mass spectrometry. J. Am. Soc. Mass Spectrom. 14, 980–991.

    Article  PubMed  CAS  Google Scholar 

  160. Zimmer, J. S., Monroe, M. E., Qian, W. J., and Smith, R. D. (2006) Advances in proteomics data analysis and display using an accurate mass and time tag approach. Mass Spectrom. Rev. 25, 450–482.

    Article  PubMed  CAS  Google Scholar 

  161. Kuster, B., Schirle, M., Mallick, P., and Aebersold, R. (2005) Scoring proteomes with proteotypic peptide probes. Nat. Rev. Mol. Cell. Biol. 6, 577–583.

    Article  PubMed  CAS  Google Scholar 

  162. Kitteringham, N. R., Jenkins, R. E., Lane, C. S., Elliott, V. L., and Park, B. K. (2008) Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 877, 1229–1239.

    Google Scholar 

  163. Mallick, P., Schirle, M., Chen, S. S., Flory, M. R., Lee, H., Martin, D., Ranish, J., Raught, B., Schmitt, R., Werner, T., Kuster, B., and Aebersold, R. (2007) Computational prediction of proteotypic peptides for quantitative proteomics. Nat. Biotechnol. 25, 125–131.

    Article  PubMed  CAS  Google Scholar 

  164. Mead, J. A., Bianco, L., Ottone, V., Barton, C., Kay, R. G., Lilley, K. S., Bond, N. J., and Bessant, C. (2008) MRMaid: the webbased tool for designing multiple reaction monitoring (MRM) transitions. Mol. Cell. Proteomics 8, 696–705.

    Google Scholar 

  165. Walsh, G. M., Lin, S., Evans, D. M., Khosrovi-Eghbal, A., Beavis, R. C., and Kast, J. (2008) Implementation of a data repository-driven approach for targeted proteomics experiments by multiple reaction monitoring. J Proteomics 72, 838–852.

    Google Scholar 

  166. Fusaro, V. A., Mani, D. R., Mesirov, J. P., and Carr, S. A. (2009) Prediction of high-responding peptides for targeted protein assays by mass spectrometry. Nat. Biotechnol. 27, 190–198.

    Article  PubMed  CAS  Google Scholar 

  167. Rifai, N., Gillette, M. A., and Carr, S. A. (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat. Biotechnol. 24, 971–983.

    Article  PubMed  CAS  Google Scholar 

  168. Ishihama, Y., Oda, Y., Tabata, T., Sato, T., Nagasu, T., Rappsilber, J., and Mann, M. (2005) Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol. Cell. Proteomics 4, 1265–1272.

    Article  PubMed  CAS  Google Scholar 

  169. Lu, P., Vogel, C., Wang, R., Yao, X., and Marcotte, E. M. (2007) Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nat. Biotechnol. 25, 117–124.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Proteomics Laboratory, EGA Institute for Women’s Health, University College London, London, UK

    John F. Timms

  2. Analytical Signalling Group, Centre for Cell Signalling, Institute of Cancer, Bart’s and the London School of Medicine, Queen Mary University of London, London, UK

    Pedro R. Cutillas

Authors
  1. John F. Timms
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pedro R. Cutillas
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Bart’s and the London School of Medicine, Institute of Cancer, Queen Mary, Universtiy of London, Charterhouse Square, London, EC1M 6BQ, United Kingdom

    Pedro R. Cutillas

  2. , EGA Institute for Women's Health, University College London, Gower Street, London, WC1E 6BT, United Kingdom

    John F. Timms

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Timms, J.F., Cutillas, P.R. (2010). Overview of Quantitative LC-MS Techniques for Proteomics and Activitomics. In: Cutillas, P., Timms, J. (eds) LC-MS/MS in Proteomics. Methods in Molecular Biology, vol 658. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-780-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-780-8_2

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-779-2

  • Online ISBN: 978-1-60761-780-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation