Mapping the human plasma proteome by SCX-LC-IMS-MS

  • Xiaoyun Liu
  • Stephen J. Valentine
  • Manolo D. Plasencia
  • Sarah Trimpin
  • Stephen Naylor
  • David E. ClemmerEmail author
Focus: From Mobilities To Proteomes


The advent of on-line multidimensional liquid chromatography-mass spectrometry has significantly impacted proteomic analyses of complex biological fluids such as plasma. However, there is general agreement that additional advances to enhance the peak capacity of such platforms are required to enhance the accuracy and coverage of proteome maps of such fluids. Here, we describe the combination of strong-cation-exchange and reversed-phase liquid chromatographies with ion mobility and mass spectrometry as a means of characterizing the complex mixture of proteins associated with the human plasma proteome. The increase in separation capacity associated with inclusion of the ion mobility separation leads to generation of one of the most extensive proteome maps to date. The map is generated by analyzing plasma samples of five healthy humans; we report a preliminary identification of 9087 proteins from 37,842 unique peptide assignments. An analysis of expected false-positive rates leads to a high-confidence identification of 2928 proteins. The results are catalogued in a fashion that includes positions and intensities of assigned features observed in the datasets as well as pertinent identification information such as protein accession number, mass, and homology score/confidence indicators. Comparisons of the assigned features reported here with other datasets shows substantial agreement with respect to the first several hundred entries; there is far less agreement associated with detection of lower abundance components.


Drift Tube Drift Time Peak Capacity Plasma Proteome Human Plasma Proteome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

13361_2011_180701249_MOESM1_ESM.pdf (3.7 mb)
Supplementary material, approximately 3871 KB.
13361_2011_180701249_MOESM2_ESM.pdf (1.2 mb)
Supplementary material, approximately 1282 KB.
13361_2011_180701249_MOESM3_ESM.pdf (58 kb)
Supplementary material, approximately 59 KB.
13361_2011_180701249_MOESM4_ESM.pdf (77 kb)
Supplementary material, approximately 79 KB.
13361_2011_180701249_MOESM5_ESM.pdf (63 kb)
Supplementary material, approximately 64 KB.


  1. 1.
    Wasinger, V. C.; Cordwell, S. J.; Cerpa-Poljak, A.; Yan, J. X.; Gooley, A. A.; Wilkins, M. R.; Duncan, M. W.; Harris, R.; Williams, K. L.; Humphery-Smith, I. Progress with Gene-Product Mapping of the Mollicutes: Mycoplasma Genitalium. Electrophoresis 1995, 16, 1090–1094.CrossRefGoogle Scholar
  2. 2.
    Hancock, W. S.; Apffel, A. J.; Chakel, J. A.; Hahnenberger, K. C.; Choudhary, G.; Traina, J.; Pungor, E. Integrated Genomic/Proteomic Analysis. Anal. Chem. 1999, 71, 742A-748A.CrossRefGoogle Scholar
  3. 2.(a)
    Schweitzer, B.; Kingsmore, S. F. Measuring Proteins on Microarrays. Curr. Opin. Biotech. 2002, 13, 14–19.CrossRefGoogle Scholar
  4. 2.(b)
    Figeys, D. Proteomics in 2002: A Year of Technical Development and Wide-Ranging Applications. Anal. Chem. 2003, 75, 2891–2905.CrossRefGoogle Scholar
  5. 2.(c)
    Romijn, E. P.; Krijgsveld, J.; Heck, A. J. R. Recent Liquid Chromatographic-(Tandem) Mass Spectrometric Applications in Proteomics. J. Chromatogr. A 2003, 1000, 589–608.CrossRefGoogle Scholar
  6. 2.(d)
    Aebersold, R.; Mann, M. Mass Spectrometry-Based Proteomics. Nature 2003, 422, 198–207.CrossRefGoogle Scholar
  7. 2.(e)
    Page, J. S.; Masselon, C. D.; Smith, R. D. FTICR Mass Spectrometry for Qualitative and Quantitative Bioanalyses. Curr. Opin. Biotech. 2004, 15, 3–11.CrossRefGoogle Scholar
  8. 2.(f)
    Anderson, L. Candidate-Based Proteomics in the Search for Biomarkers of Cardiovascular Disease. J. Physiol. (London) 2005, 563, 23–60.CrossRefGoogle Scholar
  9. 3.
    Anderson, N. L.; Anderson, N. G. The Human Plasma Proteome: History, Character, and Diagnostic Prospects. Mol. Cell. Proteom. 2002, 1, 845–867.CrossRefGoogle Scholar
  10. 4.
    Liu, X.; Plasencia, M.; Ragg, S.; Valentine, S. J.; Clemmer, D. E. Development of High-Throughput Dispersive LC-Ion Mobility-TOFMS Techniques for Analyzing the Human Plasma Proteome. Brief Funct Genomic Proteomic 2004, 3, 177–186.CrossRefGoogle Scholar
  11. 5. Scholar
  12. 6.
    Tirumalai, R. S.; Chan, K. C.; Prieto, D. A.; Issaq, H. J.; Conrads, T. P.; Veenstra, T. D. Characterization of the Low Molecular Weight Human Serum Proteome. Mol. Cell. Proteom. 2003, 2, 1096–1103.CrossRefGoogle Scholar
  13. 7.
    Putnam, F. W., Ed. The Plasma Proteins: Structure, Function and Genetic Control; Academic Press: New York, 1975.Google Scholar
  14. 8.
    Counterman, A. E.; Hilderbrand, A. E.; Srebalus Barnes, C. A.; Clemmer, D. E. Formation of Peptide Aggregates during ESI: Size, Charge, Composition, and Contributions to Noise. J. Am. Soc. Mass Spectrom. 2001, 12, 1020–1035.CrossRefGoogle Scholar
  15. 9.
    Valentine, S. J.; Plasencia, M. D.; Liu, X.; Krishnan, M.; Naylor, S.; Udseth, H. R.; Smith, R. D.; Clemmer, D. E. Toward Plasma Proteome Profiling with Ion Mobility-Mass Spectrometry. J. Proteome Res. 2006, 5, 2977–2984.CrossRefGoogle Scholar
  16. 10.
    Anderson, N. L.; Anderson, N. G. A Two-Dimensional Gel Database of Human Plasma Proteins. Electrophoresis 1991, 12, 883–906.CrossRefGoogle Scholar
  17. 11.
    Ueno, I.; Sakai, T.; Yamaoka, M.; Yoshida, R.; Tsugita, A. Analysis of Blood Plasma Proteins in Patients with Alzheimer’s Disease by Two-Dimensional Electrophoresis, Sequence Homology, and Immunodetection. Electrophoresis 2000, 21, 1832–1845.CrossRefGoogle Scholar
  18. 12.
    Pieper, R.; Gatlin, C. L.; Makusky, A. J.; Russo, P. S.; Schatz, C. R.; Miller, S. S.; Su, Q.; McGrath, A. M.; Estock, M. A.; Parmar, P. P.; Zhao, M.; Huang, S. T.; Zhou, J.; Wang, F.; Esquer-Blasco, R.; Anderson, N. L.; Taylor, J.; Steiner, S. The Human Serum Proteome: Display of Nearly 3700 Chromatographically Separated Protein Spots on Two-Dimensional Electrophoresis Gels and Identification of 325 Distinct Proteins. Proteomics 2003, 3, 1345–1364.CrossRefGoogle Scholar
  19. 13.
    Anderson, L.; Anderson, N. G. High Resolution Two-Dimensional Electrophoresis of Human Plasma Proteins. Proc. Natl. Acad. Sci. U.S.A. 1977, 74, 5421–5425.CrossRefGoogle Scholar
  20. 14.
    Dunn, M. J. Two-Dimensional Gel Electrophoresis of Proteins. J. Chromatogr. 1987, 418, 145–185.CrossRefGoogle Scholar
  21. 15.
    Anderson, N. L.; Polanski, M.; Pieper, R.; Gatlin, T.; Tirumalai, R. S.; Conrads, T. P.; Veenstra, T. D.; Adkins, J. N.; Pounds, J. G.; Fagan, R.; Lobley, A. The Human Plasma Proteome: A Nonredundant List Developed by Combination of Four Separate Sources. Mol. Cell. Proteom. 2004, 3, 311–326.CrossRefGoogle Scholar
  22. 16.
    Wolters, D. A.; Washburn, M. P.; Yates, J. R. An Automated Multidimensional Protein Identification Technology for Shotgun Proteomics. Anal. Chem. 2001, 73, 5683–5690.CrossRefGoogle Scholar
  23. 17.
    Washburn, M. P.; Wolters, D.; Yates, J. R. Large-Scale Analysis of the Yeast Proteome by Multidimensional Protein Identification Technology. Nat. Biotechnol. 2001, 19, 242–247.CrossRefGoogle Scholar
  24. 18.
    Peng, J.; Elias, J. E.; Thoreen, C. C.; Licklider, L. J.; Gygi, S. P. Evaluation of Multidimensional Chromatography Coupled with Tandem Mass Spectrometry (LC/LC-MS/MS) for Large-Scale Protein Analysis: The Yeast Proteome. J. Proteome Res. 2003, 2, 43–50.CrossRefGoogle Scholar
  25. 19.
    Adkins, J. N.; Varnum, S. M.; Auberry, K. J.; Moore, R. J.; Angell, N. H.; Smith, R. D.; Springer, D. L.; Pounds, J. G. Toward a Human Blood Serum Proteome: Analysis by Multidimensional Separation Coupled with Mass Spectrometry. Mol. Cell. Proteom. 2002, 1, 947–955.CrossRefGoogle Scholar
  26. 20.
    Wu, S. L.; Choudhary, G.; Ramstrom, M.; Bergquist, J.; Hancock, W. S. Evaluation of Shotgun Sequencing for Proteomic Analysis of Human Plasma Using HPLC Coupled with either Ion Trap or Fourier Transform Mass Spectrometry. J. Proteome Res. 2003, 2, 383–393.CrossRefGoogle Scholar
  27. 21.
    Shen, Y.; Jacobs, J. M.; Camp, D. G., II; Fang, R.; Moore, R. J.; Smith, R. D.; Xiao, W.; Davis, R. W.; Tompkins, R. G. Ultra-High-Efficiency Strong Cation Exchange LC/RPLC/MS/MS for High Dynamic Range Characterization of the Human Plasma Proteome. Anal. Chem. 2004, 76, 1134–1144.CrossRefGoogle Scholar
  28. 22.
    Zhou, M.; Lucas, D. A.; Chan, K. C.; Issaq, H. J.; Petricoin, E. F.; Liotta, L. A.; Veenstra, T. D.; Conrads, T. R. An Investigation into the Human Serum “Interactome”. Electrophoresis 2004, 25, 1289–1298.CrossRefGoogle Scholar
  29. 23.
    Rose, K.; Bougueleret, L.; Baussant, T.; Böhm, G.; Botti, P.; Colinge, J.; Cusin, I.; Gaertner, H.; Gleizes, A.; Heller, M.; Jimenez, S.; Johnson, A.; Kussmann, M.; Menin, L.; Menzel, C.; Ranno, F.; Rodriguez-Tomé, P.; Rogers, J.; Saudrais, C.; Villain, M.; Wetmore, D.; Bairoch, A.; Hochstrasser, D. Industrial-Scale Proteomics: From Liters of Plasma to Chemically Synthesized Proteins. Proteomics 2004, 4, 2125–2150.CrossRefGoogle Scholar
  30. 24.
    Proteomics 2005, 13 (entire issue). Plasma Proteome Project (PPP) collaboration sponsored by the Human Proteome Organization (HUPO), Proteomics.Google Scholar
  31. 25.
    Omenn, G. S.; States, D. J.; Adamski, M.; Blackwell, T. W.; Menon, R.; Hermjakob, H.; Apweiler, R.; Haab, B. B.; Simpson, R. J.; Eddes, J. S.; Kapp, E. A.; Moritz, R. L.; Chan, D. W.; Rai, A. J.; Admon, A.; Aebersold, R.; Eng, J.; Hancock, W. S.; Hefta, S. A.; Meyer, H.; Paik, Y.; Yoo, J.; Ping, P.; Pounds, J.; Adkins, J.; Qian, X.; Wang, R.; Wasinger, V.; Wu, C. Y.; Zhao, X.; Zeng, R.; Archakov, A.; Tsugita, A.; Beer, I.; Pandey, A.; Pisano, M.; Andrews, P.; Tammen, H.; Speicher, D. W.; Hanash, S. M. Overview of the HUPO Plasma Proteome Project: Results from the Pilot Phase with 35 Collaborating Laboratories and Multiple Analytical Groups, Generating a Core Dataset of 3020 Proteins and a Publicly-Available Database. Proteomics 2005, 5, 3226–3245.CrossRefGoogle Scholar
  32. 26.
    Chan, K. C.; Lucas, D. A.; Hise, D.; Schaefer, C. F.; Xiao, Z.; Janini,. George, M.; Buetow, K. H.; Issaq, H. J.; Veenstra, T. D.; Conrads, T. P. Analysis of the Human Serum Proteome. Clin. Proteom. 2004, 1, 101–226.CrossRefGoogle Scholar
  33. 27.
    Jiang, L.; He, L.; Fountoulakis, M. Comparison of Protein Precipitation Methods for Sample Preparation Prior to Proteomic Analysis. J. Chromatogr. A 2004, 1023, 317–320.CrossRefGoogle Scholar
  34. 28.
    Hsieh, S. Y.; Chen, R. K.; Pan, Y. H.; Lee, H. L. Systematical Evaluation of the Effects of Sample Collection Procedures on Low-Molecular-Weight Serum/Plasma Proteome Profiling. Proteomics 2006, 6, 3189–3198.CrossRefGoogle Scholar
  35. 29.
    Liu, T.; Qian, W.-J.; Mottaz, H. M.; Gritsenko, M. A.; Norbeck, A. D.; Moore, R. J.; Purvine, S. O.; Camp, D. G., II; Smith, R. D. Evaluation of Multiprotein Immunoaffinity Subtraction for Plasma Proteomics and Candidate Biomarker Discovery Using Mass Spectrometry. Mol. Cell. Proteom. 2006, 5, 2167–2174.CrossRefGoogle Scholar
  36. 30.
    Banks, R. E.; Stanley, A. J.; Cairns, D. A.; Barrett, J. H.; Clarke, P.; Thompson, D.; Selby, P. J. Influences of Blood Sample Processing on Low-Molecular-Weight Proteome Identified by Surface-Enhanced Laser Desorption/Ionization Mass Spectrometry. Clin. Chem. 2005, 51, 1637–1649.CrossRefGoogle Scholar
  37. 31.
    Stone, E.; Gillig, K. J.; Ruotolo, B.; Fuhrer, K.; Gonin, M.; Schultz, A.; Russell, D. H. Surface-Induced Dissociation on a MALDI-Ion Mobility-Orthogonal Time-of-Flight Mass Spectrometer: Sequencing Peptides from an “In-Solution” Protein Digest. Anal. Chem. 2001, 73, 2233–2238.CrossRefGoogle Scholar
  38. 32.
    Wysocki, V. H.; Resing, K. A.; Zhang, Q. F.; Cheng, G. L. Mass Spectrometry of Peptides and Proteins. Methods 2005, 35, 211–222.CrossRefGoogle Scholar
  39. 33.
    Mikesh, L. M.; Ueberheide, B.; Chi, A.; Coon, J. J.; Syka, J. E.; Shabanowitz, J.; Hunt, D. F. The Utility of ETD Mass Spectrometry in Proteomic Analysis. Biochim. Biophys. Acta 2006, 1764, 1811–1822.CrossRefGoogle Scholar
  40. 34.
    Dodds, E. D.; Hagerman, P. J.; Lebrilla, C. B. Fragmentation of Singly Protonated Peptides via a Combination of Infrared and Collisional Activation. Anal. Chem. 2006, 78, 8506–8511.CrossRefGoogle Scholar
  41. 35.
    Zubarev, R. Protein Primary Structure Using Orthogonal Fragmentation Techniques in Fourier Transform Mass Spectrometry. Expert. Rev. Proteom. 2006, 3, 251–261.CrossRefGoogle Scholar
  42. 36.
    Bakhtiar, R.; Guan, Z. Q. Electron Capture Dissociation Mass Spectrometry in Characterization of Peptides and Proteins. Biotechnol. Lett. 2006, 28, 1047–1059.CrossRefGoogle Scholar
  43. 37.
    Fernandez, F. M.; Wysocki, V. H.; Futrell, J. H.; Laskin, J. Protein Identification via Surface-Induced Dissociation in an FT-ICR Mass Spectrometer and a Patchwork Sequencing Approach. J. Am. Soc. Mass Spectrom. 2006, 17, 700–709.CrossRefGoogle Scholar
  44. 38.
    Riter, L. S.; Gooding, K. M.; Hodge, B. D.; Julian, R. K. Comparison of the Paul Ion Trap to the Linear Ion Trap for Use in Global Proteomics. Proteomics 2006, 6, 1735–1740.CrossRefGoogle Scholar
  45. 39.
    Jacobs, J. M.; Adkins, J. N.; Qian, W. J.; Shen, Y.; Camp, D. G., II; Smith, R. D. Utilizing Human Blood Plasma for Proteomic Biomarker Discovery. J. Proteome Res. 2005, 4, 1073–1085.CrossRefGoogle Scholar
  46. 40.
    Cargile, B. J.; Bundy, J. L.; Stephenson, J. L., Jr. Potential for False Positive Identifications from Large Databases through Tandem Mass Spectrometry. J. Proteome Res. 2004, 3, 1082–1085.CrossRefGoogle Scholar
  47. 41.
    Kapp, E. A.; Schutz, F.; Connolly, L. M.; Chakel, J. A.; Meza, J. E.; Miller, C. A.; Fenyo, D.; Eng, J. K.; Adkins, J. N.; Omenn, G. S.; Simpson, R. J. An Evaluation, Comparison, and Accurate Benchmarking of Several Publicly Available MS/MS Search Algorithms: Sensitivity and Specificity Analysis. Proteomics 2005, 5, 3475–3490.CrossRefGoogle Scholar
  48. 42.
    States, D. J.; Omenn, G. S.; Blackwell, T. W.; Fermin, D.; Eng, J.; Speicher, D. W.; Hanash, S. M. Challenges in Deriving High-Confidence Protein Identifications from Data Gathered by a HUPO Plasma Proteome Collaborative Study. Nat. Biotechnol. 2006, 24, 333–338.CrossRefGoogle Scholar
  49. 43.
    St. Louis, R. H.; Hill, H. H. Ion Mobility Spectrometry in Analytical Chemistry. CRC Crit. Rev. Anal. Chem. 1990, 21, 321–355.CrossRefGoogle Scholar
  50. 44.
    Clemmer, D. E.; Hudgins, R. R.; Jarrold, M. F. Naked Protein Conformations: Cytochrome c in the Gas Phase. J. Am. Chem. Soc. 1995, 117, 10141–10142.CrossRefGoogle Scholar
  51. 45.
    von Helden, G.; Wyttenbach, T.; Bowers, M. T. Conformation of Macromolecules in the Gas Phase: Use of Matrix-Assisted Laser Desorption Methods in Ion Chromatography. Science 1995, 267, 1483–1485.CrossRefGoogle Scholar
  52. 46.
    Chen, Y. H.; Hill, H. H.; Wittmer, D. P. Thermal Effects on Electrospray Ionization Ion Mobility Spectrometry. Int. J. Mass Spectrom. Ion Processes 1996, 154, 1–13.CrossRefGoogle Scholar
  53. 47.
    Gillig, K. J.; Ruotolo, B.; Stone, E. G.; Russell, D. H.; Fuhrer, K.; Gonin, M.; Schultz, A. J. Coupling High-Pressure MALDI with Ion Mobility/Orthogonal Time-of-Flight Mass Spectrometry. Anal. Chem. 2000, 72, 3965–3971.CrossRefGoogle Scholar
  54. 48.
    Steiner, W. E.; Clowers, B. H.; English, W. A.; Hill, H. H., Jr. Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization with Analysis by Ion Mobility Time-of-Flight Mass Spectrometry. Rapid Commun. Mass Spectrom. 2004, 18, 882–888.CrossRefGoogle Scholar
  55. 49.
    Myung, S.; Wiseman, J. M.; Valentine, S. J.; Zoltán, T.; Cooks, R. G.; Clemmer, D. E. Coupling Desorption Electrospray Ionization (DESI) with Ion Mobility/Mass Spectrometry for Analysis of Protein Structure: Evidence for Desorption of Folded and Denatured States. J. Phys. Chem. B 2006, 110, 5045–5051.CrossRefGoogle Scholar
  56. 50.
    Shaffer, S. A.; Prior, D. C.; Anderson, G. A.; Udseth, H. R.; Smith, R. D. An Ion Funnel Interface for Improved Ion Focusing and Sensitivity Using Electrospray Ionization Mass Spectrometry. Anal. Chem. 1998, 70, 4111–4119.CrossRefGoogle Scholar
  57. 51.
    Kim, T.; Tolmachev, A. V.; Harkewicz, R.; Prior, D. C.; Anderson, G.; Udseth, H. R.; Smith, R. D.; Bailey, T. H.; Rakov, S.; Futrell, J. H. Design and Implementation of a New Electrodynamic Ion Funnel. Anal. Chem. 2000, 72, 2247–2255.CrossRefGoogle Scholar
  58. 52.
    Lee, Y. J.; Hoaglund-Hyzer, C. S.; Taraszka, J. A.; Zientara, G. A.; Counterman, A. E.; Clemmer, D. E. Collision-Induced Dissociation of Mobility-Separated Ions Using an Orifice-Skimmer Cone at the Back of a Drift Tube. Anal. Chem. 2001, 73, 3549–3555.CrossRefGoogle Scholar
  59. 53.
    Tang, K.; Shvartsburg, A. A.; Lee, H.; Prior, D. C.; Buschbach, M. A.; Li, F.; Tomachev, A.; Anderson, G. A.; Smith, R. D. High-Sensitivity Ion Mobility Spectrometry/Mass Spectrometry Using Electrodynamic Ion Funnel Interfaces. Anal. Chem. 2005, 77, 3330–3339.CrossRefGoogle Scholar
  60. 54.
    Myung, S.; Lee, Y. L.; Moon, M. H.; Taraszka, J. A.; Sowell, R.; Koeniger, S. L.; Hilderbrand, A. E.; Valentine, S. J.; Cherbas, L.; Cherbas, P.; Kaufmann, T. C.; Miller, D. F.; Mechref, Y.; Novotny, M. V.; Ewing, M.; Clemmer, D. E. Development of High-Sensitivity Ion Trap-IMS-TOF Techniques: A High-Throughput Nano-LC/IMS/TOF Separation of the Drosophila Fly Proteome. Anal. Chem. 2003, 75, 5137–5145.CrossRefGoogle Scholar
  61. 55.
    McLean, J. A.; Russell, D. H. Sub-Femtomole Peptide Detection in Ion Mobility-Time-of-Flight Mass Spectrometry Measurements. J. Proteome Res. 2003, 2, 427–430.CrossRefGoogle Scholar
  62. 56.
    Dugourd, P.; Hudgins, R. R.; Clemmer, D. E.; Jarrold, M. F. High-Resolution Ion Mobility Measurements. Rev. Sci. Instrum. 1997, 68, 1122–1129.CrossRefGoogle Scholar
  63. 57.
    Wu, C.; Siems, W. F.; Asbury, G. R.; Hill, H. H., Jr. Electrospray Ionization High-Resolution Ion Mobility Spectrometry-Mass Spectrometry. Anal. Chem. 1998, 70, 4929–4938.CrossRefGoogle Scholar
  64. 58.
    Srebalus, C. A.; Li, J.; Marshall, W. S.; Clemmer, D. E. Gas-Phase Separations of Electrosprayed Peptide Libraries. Anal. Chem. 1999, 71, 3918–3927.CrossRefGoogle Scholar
  65. 59.
    Valentine, S. J.; Counterman, A. E.; Hoaglund-Hyzer, C. S.; Clemmer, D. E. Intrinsic Amino Acid Size Parameters from a Series of 113 Lysine-Terminated Tryptic Digest Peptide Ions. J. Phys. Chem. B 1999, 103, 1203–1207.CrossRefGoogle Scholar
  66. 60.
    Shvartsburg, A. A.; Siu, K. W. M.; Clemmer, D. E. Prediction of Peptide Ion Mobilities via a priori Calculations from Intrinsic Size Parameters of Amino Acid Residues. J. Am. Soc. Mass Spectrom. 2001, 12, 885–888.CrossRefGoogle Scholar
  67. 61.
    Valentine, S. J.; Counterman, A. E.; Clemmer, D. E. A Database of 660 Peptide Ion Cross Sections: Use of Intrinsic Size Parameters for Bona Fide Predictions of Cross Sections. J. Am. Soc. Mass Spectrom. 1999, 10, 1188–1211.CrossRefGoogle Scholar
  68. 62.
    Mosier, P. D.; Counterman, A. E.; Jurs, P. C.; Clemmer, D. E. Prediction of Peptide Ion Collision Cross Sections from Topological Molecular Structure and Amino Acid Parameters. Anal. Chem. 2002, 74, 1360–1370.CrossRefGoogle Scholar
  69. 63.
    Wyttenbach, T.; von Helden, G.; Batka, J. J., Jr.; Carlat, D.; Bowers, M. T. Effect of the Long-Range Potential on Ion Mobility Measurements. J. Am. Soc. Mass Spectrom. 1997, 8, 275–282.CrossRefGoogle Scholar
  70. 64.
    Shvartsburg, A. A.; Jarrold, M. F. An Exact Hard-Sphere Scattering Model for the Mobilities of Polyatomic Ions. Chem. Phys. Lett. 1996, 261, 86–91.CrossRefGoogle Scholar
  71. 65.
    Mesleh, M. F.; Hunter, J. M.; Shvartsburg, A. A.; Schatz, G. C.; Jarrold, M. F. Structural Information from Ion Mobility Measurements: Effects of the Long-Range Potential. J. Phys. Chem. 1996, 100, 16082–16086.CrossRefGoogle Scholar
  72. 66.
    Clemmer, D. E.; Jarrold, M. F. Ion Mobility Measurements and their Applications to Clusters and Biomolecules. J. Mass Spectrom. 1997, 32, 577–592.CrossRefGoogle Scholar
  73. 67.
    Hoaglund-Hyzer, C. S.; Counterman, A. E.; Clemmer, D. E. Anhydrous Protein Ions. Chem. Rev. 1999, 99, 3037–3079.CrossRefGoogle Scholar
  74. 68.
    Wyttenbach, T.; Bowers, M. T. Gas-Phase Conformations: The Ion Mobility/Ion Chromatography Method. Modern Mass Spectrom. Topics Curr. Chem. Chemistry and Materials Science; Springer: Berlin/Heidelberg, 2003, 225, 207–232.Google Scholar
  75. 69.
    Study number 05-10163, Indiana University Institutional Review Board.Google Scholar
  76. 70.
    Multiple affinity removal LC column—Human 6 Agilent Technologies, Scholar
  77. 71.
    Valentine, S. J.; Koeniger, S. L.; Clemmer, D. E. A Split-Field Drift Tube for Separation and Efficient Fragmentation of Biomolecular Ions. Anal. Chem. 2003, 75, 6202–6208.CrossRefGoogle Scholar
  78. 72.
    Taraszka, J. A.; Kurulugama, R.; Sowell, R.; Valentine, S. J.; Koeniger, S. L.; Arnold, R. J.; Miller, D. F.; Kaufman, T. C.; Clemmer, D. E. Mapping the Proteome of Drosophila Melanogaster: Analysis of Embryos and Adult Heads by LC-IMS-MS Methods. J. Proteome Res. 2005, 4, 1223–1237.CrossRefGoogle Scholar
  79. 73.
    Collins, D. C.; Lee, M. L. Developments in Ion Mobility Spectrometry-Mass Spectrometry. Anal. Bioanal. Chem. 2002, 372, 66–73.CrossRefGoogle Scholar
  80. 74.
    Wittmer, D.; Chen, Y. H.; Luckenbill, B. K.; Hill, H. H., Jr. Electrospray-Ionization Ion Mobility Spectrometry. Anal. Chem. 1994, 66, 2348–2355.CrossRefGoogle Scholar
  81. 75.
    Valentine, S. J.; Counterman, A. E.; Hoaglund, C. S.; Reilly, J. P.; Clemmer, D. E. Gas-Phase Separations of Protease Digests. J. Am. Soc. Mass Spectrom. 1998, 9, 1213–1216.CrossRefGoogle Scholar
  82. 76.
    Hoaglund, C. S.; Valentine, S. J.; Sporleder, C. R.; Reilly, J. P.; Clemmer, D. E. Three-Dimensional Ion Mobility/TOFMS Analysis of Electrosprayed Biomolecules. Anal. Chem. 1998, 70, 2236–2242.CrossRefGoogle Scholar
  83. 77.
    Perkins, D. N.; Pappin, D. J. C.; Creasy, D. M.; Cottrell, J. S. Probability-Based Protein Identification by Searching Sequence Databases Using Mass Spectrometry Data. Electrophoresis 1999, 20, 3551–3567.CrossRefGoogle Scholar
  84. 78.
    The protein database is searched using the enzyme trypsin and allowing for a single missed cleavage. A single fixed (carbamidomethyl) modification for cysteine residues is used as a search parameter. Peptides with homology scores above the identity threshold (31) are saved for map consideration.Google Scholar
  85. 79.
    Hoaglund-Hyzer, C. S.; Li, J.; Clemmer, D. E. Mobility Labeling for Parallel CID of Ion Mixtures. Anal. Chem. 2000, 72, 2737–2740.CrossRefGoogle Scholar
  86. 80., Specialty Laboratories website.Google Scholar
  87. 81., Technical notes for Agilent LC MSD TOF.Google Scholar
  88. 82.
    Keller, A.; Nesvizhskii, A. I.; Kolker, E.; Aebersold, R. Empirical Statistical Model to Estimate the Accuracy of Peptide Identifications Made by MS/MS and Database Search. Anal. Chem. 2002, 74, 5383–5392.CrossRefGoogle Scholar
  89. 83.
    Peng, J.; Elias, J. E.; Thoreen, C. C.; Licklidder, L. J.; Gygi, S. P. Evaluation of Multidimensional Chromatography Coupled with Tandem Mass Spectrometry (LC/LC-MS/MS) for Large-Scale Protein Analysis: The Yeast Proteome. J. Proteome Res. 2003, 2, 43–50.CrossRefGoogle Scholar
  90. 84.
    Elias, J. E.; Gibbons, F. D.; King, O. D.; Roth, F. P.; Gygi, S. P. Intensity-Based Protein Identification by Machine Learning from a Library of Tandem Mass Spectra. Nat. Biotechnol. 2004, 22, 214–219.CrossRefGoogle Scholar
  91. 85.
    Park, G. W.; Kwon, K. H.; Kim, J. Y.; Lee, J. H.; Yun, S. H.; Kim, S. I.; Park, Y. M.; Cho, S. Y.; Paik, Y. K.; Yoo, J. S. Human Plasma Proteome Analysis by Reversed Sequence Database Search and Molecular Weight Correction Based on a Bacterial Proteome Analysis. Proteomics 2006, 6, 1121–1132.CrossRefGoogle Scholar
  92. 86.
    Cargile, B. J.; Bundy, J. L.; Grunden, A. M.; Stephenson, J. L., Jr. Synthesis/Degradation Ratio Mass Spectrometry for Measuring Relative Dynamic Protein Turnover. Anal. Chem. 2004, 76, 86–97.CrossRefGoogle Scholar
  93. 87.
    Bruce, J. E.; Anderson, G. A.; Smith, R. D. “Colored” Noise Waveforms and Quadrupole Excitation for the Dynamic Range Expansion of Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Anal. Chem. 1996, 68, 534–541.CrossRefGoogle Scholar
  94. 88., Thermo Electron Corporation Application Notes.Google Scholar
  95. 89., Thermo Electron Corporation Application Notes.Google Scholar
  96. 90.
    Derkx, F. H.; Schalekamp, M. P.; Bouma, B.; Kluft, C.; Schalekamp, M. A. Plasma Kallikrein-Mediated Activation of the Renin-Angiotensin System Does Not Require Prior Acidification of Prorenin. J. Clin. Endocrinol. Metab. 1982, 54, 343–348.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2007

Authors and Affiliations

  • Xiaoyun Liu
    • 1
  • Stephen J. Valentine
    • 2
  • Manolo D. Plasencia
    • 1
  • Sarah Trimpin
    • 1
  • Stephen Naylor
    • 2
  • David E. Clemmer
    • 1
    Email author
  1. 1.Department of ChemistryIndiana UniversityBloomingtonUSA
  2. 2.Predictive Physiology and Medicine Inc.BloomingtonUSA

Personalised recommendations