Skip to main content

Stable Isotope Labeling Methods in Protein Profiling

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1023))

Abstract

Mass spectrometry (MS) analysis of peptides and proteins has evolved dramatically over the last 20 years. Improvement of MS instrumentation, computational data analysis, and the availability of complete sequence databases for many species have made large-scale proteomics analyses possible. The measurement of global protein abundance by quantitative mass spectrometry has the potential to increase both speed and impact of biological and clinical research. However, to be able to detect and identify potential biomarkers, reproducible and accurate quantification is essential.

The following chapter describes how to perform quantitative protein profiling using stable isotope labeling methods. Throughout, there is a focus on guidance in selection of an appropriate labeling strategy. With that in mind, we have included a section on acquisition and understanding of the liquid chromatography-mass spectrometry (LC-MS) data format.

Further, we describe the different stable isotope labeling methods and their pros and cons. We start by giving an overview of the overall quantitative proteomics workflow in which extracting relevant biological information from the acquired data is the ultimate goal.

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

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
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

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Aebersold R (2009) A stress test for mass spectrometry-based proteomics. Nat Methods 6:411–412

    Article  PubMed  CAS  Google Scholar 

  2. Nilsson T, Mann M, Aebersold R, Yates JR III, Bairoch A, Bergeron JJ (2010) Mass spectrometry in high-throughput proteomics: ready for the big time. Nat Methods 7:681–685

    Article  PubMed  CAS  Google Scholar 

  3. Nagaraj N, Kulak NA, Cox J, Neuhauser N, Mayr K, Hoerning O, Vorm O, Mann M (2012) System-wide perturbation analysis with nearly complete coverage of the yeast proteome by single-shot ultra HPLC runs on a bench top Orbitrap. Mol Cell Proteomics 11(M111):013722

    PubMed  Google Scholar 

  4. Perkins DN, Pappin DJ, Creasy DM, Cottrell JS (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20:3551–3567

    Article  PubMed  CAS  Google Scholar 

  5. Reiter L, Claassen M, Schrimpf SP, Jovanovic M, Schmidt A, Buhmann JM, Hengartner MO, Aebersold R (2009) Protein identification false discovery rates for very large proteomics data sets generated by tandem mass spectrometry. Mol Cell Proteomics 8:2405–2417

    Article  PubMed  CAS  Google Scholar 

  6. Forshed J, Pernemalm M, Branca RM, Sandberg A, Lehtiö J (2011) Enhanced information and improved accuracy from shotgun proteomics by protein quantification based on peptide quality control (PQPQ). Mol Cell Proteomics 10(10):4

    Google Scholar 

  7. Zhang G, Fenyo D, Neubert TA (2009) Evaluation of the variation in sample preparation for comparative proteomics using stable isotope labeling by amino acids in cell culture. J Proteome Res 8:1285–1292

    Article  PubMed  CAS  Google Scholar 

  8. Ibarrola N, Molina H, Iwahori A, Pandey A (2004) A novel proteomic approach for specific identification of tyrosine kinase substrates using [13C]tyrosine. J Biol Chem 279:15805–15813

    Article  PubMed  CAS  Google Scholar 

  9. Martinovic S, Veenstra TD, Anderson GA, Pasa-Tolic L, Smith RD (2002) Selective incorporation of isotopically labeled amino acids for identification of intact proteins on a proteome-wide level. J Mass Spectrom 37:99–107

    Article  PubMed  Google Scholar 

  10. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, 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 

  11. Ong SE, Kratchmarova I, 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 

  12. Bendall SC, Hughes C, Stewart MH, Doble B, Bhatia M, Lajoie GA (2008) Prevention of amino acid conversion in SILAC experiments with embryonic stem cells. Mol Cell Proteomics 7:1587–1597

    Article  PubMed  CAS  Google Scholar 

  13. Kruger M, Moser M, Ussar S, Thievessen I, Luber CA, Forner F, Schmidt S, Zanivan S, Fassler R, 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  Google Scholar 

  14. Sury MD, Chen JX, Selbach M (2010) The SILAC fly allows for accurate protein quantification in vivo. Mol Cell Proteomics 9:2173–2183

    Article  PubMed  CAS  Google Scholar 

  15. Gouw JW, Krijgsveld J, Heck AJ (2010) Quantitative proteomics by metabolic labeling of model organisms. Mol Cell Proteomics 9:11–24

    Article  PubMed  CAS  Google Scholar 

  16. Geiger T, Cox J, Ostasiewicz P, Wisniewski JR, Mann M (2010) Super-SILAC mix for quantitative proteomics of human tumor tissue. Nat Methods 7:383–385

    Article  PubMed  CAS  Google Scholar 

  17. Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17:994–999

    Article  PubMed  CAS  Google Scholar 

  18. Schmidt A, Kellermann J, Lottspeich F (2005) A novel strategy for quantitative proteomics using isotope-coded protein labels. Proteomics 5:4–15

    Article  PubMed  CAS  Google Scholar 

  19. Maccarrone G, Turck CW, Martins-de-Souza D (2010) Shotgun mass spectrometry workflow combining IEF and LC-MALDI-TOF/TOF. Protein J 29:99–102

    Article  PubMed  CAS  Google Scholar 

  20. Turtoi A, Mazzucchelli GD, De Pauw E (2010) Isotope coded protein label quantification of serum proteins—comparison with the label-free LC-MS and validation using the MRM approach. Talanta 80:1487–1495

    Article  PubMed  CAS  Google Scholar 

  21. Kellermann J (2008) ICPL – isotope-coded protein label. In: Posch A (ed) 2D PAGE: sample preparation and fractionation. Humana, Totowa, NJ, pp 113–123

    Chapter  Google Scholar 

  22. Pratt JM, Simpson DM, Doherty MK, Rivers J, Gaskell SJ, Beynon RJ (2006) Multiplexed absolute quantification for proteomics using concatenated signature peptides encoded by QconCAT genes. Nat Protoc 1:1029–1043

    Article  PubMed  CAS  Google Scholar 

  23. Rivers J, Simpson DM, Robertson DH, Gaskell SJ, Beynon RJ (2007) Absolute multiplexed quantitative analysis of protein expression during muscle development using QconCAT. Mol Cell Proteomics 6:1416–1427

    Article  PubMed  CAS  Google Scholar 

  24. Eyers CE, Simpson DM, Wong SC, Beynon RJ, Gaskell SJ (2008) QCAL–a novel standard for assessing instrument conditions for proteome analysis. J Am Soc Mass Spectrom 19:1275–1280

    Article  PubMed  CAS  Google Scholar 

  25. Wiese S, Reidegeld KA, Meyer HE, Warscheid B (2007) Protein labeling by iTRAQ: a new tool for quantitative mass spectrometry in proteome research. Proteomics 7:340–350

    Article  PubMed  CAS  Google Scholar 

  26. Prudova A, auf dem Keller U, Butler GS, Overall CM (2010) Multiplex N-terminome analysis of MMP-2 and MMP-9 substrate degradomes by iTRAQ-TAILS quantitative proteomics. Mol Cell Proteomics 9:894–911

    Article  PubMed  CAS  Google Scholar 

  27. auf dem Keller U, Prudova A, Gioia M, Butler GS, Overall CM (2010) A statistics-based platform for quantitative N-terminome analysis and identification of protease cleavage products. Mol Cell Proteomics 9:912–927

    Article  PubMed  CAS  Google Scholar 

  28. Mirgorodskaya OA, Kozmin YP, Titov MI, Körner R, Sönksen CP, Roepstorff P (2000) Quantitation of peptides and proteins by matrix-assisted laser desorption/ionization mass spectrometry using 18O-labeled internal standards. Rapid Commun Mass Spectrom 14:1226–1232

    Article  PubMed  CAS  Google Scholar 

  29. Fenselau C, Yao X (2009) 18O2-Labeling in quantitative proteomic strategies: a status report. J Proteome Res 8:2140–2143

    Article  PubMed  CAS  Google Scholar 

  30. Petritis BO, Qian W-J, Camp DG, Smith RD (2009) A simple procedure for effective quenching of trypsin activity and prevention of 18O-labeling back-exchange. J Proteome Res 8:2157–2163

    Article  PubMed  CAS  Google Scholar 

  31. Sevinsky JR, Brown KJ, Cargile BJ, Bundy JL, Stephenson JL Jr (2007) Minimizing back exchange in 18O/16O quantitative proteomics experiments by incorporation of immobilized trypsin into the initial digestion step. Anal Chem 79:2158–2162

    Article  PubMed  CAS  Google Scholar 

  32. Ji C, Guo N, Li L (2005) Differential dimethyl labeling of N-termini of peptides after guanidination for proteome analysis. J Proteome Res 4:2099–2108

    Article  PubMed  CAS  Google Scholar 

  33. Boersema PJ, Aye TT, van Veen TA, Heck AJ, Mohammed S (2008) Triplex protein quantification based on stable isotope labeling by peptide dimethylation applied to cell and tissue lysates. Proteomics 8:4624–4632

    Article  PubMed  CAS  Google Scholar 

  34. Boersema PJ, Raijmakers R, Lemeer S, Mohammed S, Heck AJ (2009) Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics. Nat Protoc 4:484–494

    Article  PubMed  CAS  Google Scholar 

  35. Boersema PJ, Foong LY, Ding VM, Lemeer S, van Breukelen B, Philp R, Boekhorst J, Snel B, den Hertog J, Choo AB, Heck AJ (2010) In-depth qualitative and quantitative profiling of tyrosine phosphorylation using a combination of phosphopeptide immunoaffinity purification and stable isotope dimethyl labeling. Mol Cell Proteomics 9:84–99

    Article  PubMed  CAS  Google Scholar 

  36. Raijmakers R, Heck AJ, Mohammed S (2009) Assessing biological variation and protein processing in primary human leukocytes by automated multiplex stable isotope labeling coupled to 2 dimensional peptide separation. Mol Biosyst 5:992–1003

    Article  PubMed  CAS  Google Scholar 

  37. Kleifeld O, Doucet A, auf dem Keller U, Prudova A, Schilling O, Kainthan RK, Starr AE, Foster LJ, Kizhakkedathu JN, Overall CM (2010) Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat Biotechnol 28:281–288

    Article  PubMed  CAS  Google Scholar 

  38. Mortensen P, Gouw JW, Olsen JV, Ong S-E, Rigbolt KTG, Bunkenborg J, Cox JR, Foster LJ, Heck AJR, Blagoev B, Andersen JS, Mann M (2009) MSQuant, an open source platform for mass spectrometry-based quantitative proteomics. J Proteome Res 9:393–403

    Article  Google Scholar 

  39. Bellew M, Coram M, Fitzgibbon M, Igra M, Randolph T, Wang P, May D, Eng J, Fang R, Lin C, Chen J, Goodlett D, Whiteaker J, Paulovich A, McIntosh M (2006) A suite of algorithms for the comprehensive analysis of complex protein mixtures using high-resolution LC-MS. Bioinformatics 22:1902–1909

    Article  PubMed  CAS  Google Scholar 

  40. Cox J, Mann M (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26:1367–1372

    Article  PubMed  CAS  Google Scholar 

  41. Karp NA, Huber W, Sadowski PG, Charles PD, Hester SV, Lilley KS (2010) Addressing accuracy and precision issues in iTRAQ quantitation. Mol Cell Proteomics 9:1885–1897

    Article  PubMed  CAS  Google Scholar 

  42. Pichler P, Kocher T, Holzmann J, Mazanek M, Taus T, Ammerer G, Mechtler K (2010) Peptide labeling with isobaric tags yields higher identification rates using iTRAQ 4-plex compared to TMT 6-plex and iTRAQ 8-plex on LTQ Orbitrap. Anal Chem 82:6549–6558

    Article  PubMed  CAS  Google Scholar 

  43. Pottiez G, Wiederin J, Fox HS, Ciborowski P (2012) Comparison of 4-plex to 8-plex iTRAQ quantitative measurements of proteins in human plasma samples. J Proteome Res 11:3774–3781

    Article  PubMed  CAS  Google Scholar 

  44. Pachl F, Fellenberg K, Wagner C, Kuster B (2012) Ultra-high intra-spectrum mass accuracy enables unambiguous identification of fragment reporter ions in isobaric multiplexed quantitative proteomics. Proteomics 12:1328–1332

    Article  PubMed  CAS  Google Scholar 

  45. Ow SY, Salim M, Noirel J, Evans C, Wright PC (2011) Minimising iTRAQ ratio compression through understanding LC-MS elution dependence and high-resolution HILIC fractionation. Proteomics 11:2341–2346

    Article  PubMed  CAS  Google Scholar 

  46. Dayon L, Pasquarello C, Hoogland C, Sanchez JC, Scherl A (2010) Combining low- and high-energy tandem mass spectra for optimized peptide quantification with isobaric tags. J Proteomics 73:769–777

    Article  PubMed  CAS  Google Scholar 

  47. Kocher T, Pichler P, Schutzbier M, Stingl C, Kaul A, Teucher N, Hasenfuss G, Penninger JM, Mechtler K (2009) High precision quantitative proteomics using iTRAQ on an LTQ Orbitrap: a new mass spectrometric method combining the benefits of all. J Proteome Res 8:4743–4752

    Article  PubMed  CAS  Google Scholar 

  48. Michalski A, Damoc E, Lange O, Denisov E, Nolting D, Muller M, Viner R, Schwartz J, Remes P, Belford M, Dunyach JJ, Cox J, Horning S, Mann M, Makarov A (2012) Ultra high resolution linear ion trap orbitrap mass spectrometer (orbitrap elite) facilitates top down LC MS/MS and versatile peptide fragmentation modes. Mol Cell Proteomics 11(O111):013698

    PubMed  Google Scholar 

  49. Ow SY, Cardona T, Taton A, Magnuson A, Lindblad P, Stensjo K, Wright PC (2008) Quantitative shotgun proteomics of enriched heterocysts from Nostoc sp. PCC 7120 using 8-plex isobaric peptide tags. J Proteome Res 7:1615–1628

    Article  PubMed  CAS  Google Scholar 

  50. Engmann O, Campbell J, Ward M, Giese KP, Thompson AJ (2010) Comparison of a protein-level and peptide-level labeling strategy for quantitative proteomics of synaptosomes using isobaric tags. J Proteome Res 9:2725–2733

    Article  PubMed  CAS  Google Scholar 

  51. Dayon L, Hainard A, Licker V, Turck N, Kuhn K, Hochstrasser DF, Burkhard PR, Sanchez JC (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 

  52. Dayon L, Turck N, Kienle S, Schulz-Knappe P, Hochstrasser DF, Scherl A, Sanchez JC (2010) Isobaric tagging-based selection and quantitation of cerebrospinal fluid tryptic peptides with reporter calibration curves. Anal Chem 82:848–858

    Article  PubMed  CAS  Google Scholar 

  53. Ross PL, Huang YN, Marchese JN, 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, Pappin DJ (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3:1154–1169

    Article  PubMed  CAS  Google Scholar 

  54. Ow SY, Salim M, Noirel J, Evans C, Rehman I, Wright PC (2009) iTRAQ underestimation in simple and complex mixtures: “the good, the bad and the ugly”. J Proteome Res 8:5347–5355

    Article  PubMed  CAS  Google Scholar 

  55. Addona TA, Abbatiello SE, Schilling B, Skates SJ, Mani DR, Bunk DM, Spiegelman CH, Zimmerman LJ, Ham A-JL, Keshishian H, Hall SC, Allen S, Blackman RK, Borchers CH, Buck C, Cardasis HL, Cusack MP, Dodder NG, Gibson BW, Held JM, Hiltke T, Jackson A, Johansen EB, Kinsinger CR, Li J, Mesri M, Neubert TA, Niles RK, Pulsipher TC, Ransohoff D, Rodriguez H, Rudnick PA, Smith D, Tabb DL, Tegeler TJ, Variyath AM, Vega-Montoto LJ, Wahlander A, Waldemarson S, Wang M, Whiteaker JR, Zhao L, Anderson NL, Fisher SJ, Liebler DC, Paulovich AG, Regnier FE, Tempst P, Carr SA (2009) Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat Biotechnol 27:633–641

    Article  PubMed  CAS  Google Scholar 

  56. Fortin T, Salvador A, Charrier JP, Lenz C, Bettsworth F, Lacoux X, Choquet-Kastylevsky G, Lemoine J (2009) Multiple reaction monitoring cubed for protein quantification at the low nanogram/milliliter level in nondepleted human serum. Anal Chem 81:9343–9352

    Article  PubMed  CAS  Google Scholar 

  57. Keshishian H, Addona T, Burgess M, Mani DR, Shi X, Kuhn E, Sabatine MS, Gerszten RE, Carr SA (2009) Quantification of ­cardiovascular biomarkers in patient plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 8:2339–2349

    Article  PubMed  CAS  Google Scholar 

  58. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1:845–867

    Article  PubMed  CAS  Google Scholar 

  59. Anderson L, Hunter CL (2006) Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins. Mol Cell Proteomics 5:573–588

    PubMed  CAS  Google Scholar 

  60. Keshishian H, Addona T, Burgess M, Kuhn E, Carr SA (2007) Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 6:2212–2229

    Article  PubMed  CAS  Google Scholar 

  61. Anderson NL, Anderson NG, Haines LR, Hardie DB, Olafson RW, Pearson TW (2004) Mass spectrometric quantitation of peptides and proteins using stable isotope standards and capture by anti-peptide antibodies (SISCAPA). J Proteome Res 3:235–244

    Article  PubMed  CAS  Google Scholar 

  62. Kuhn E, Addona T, Keshishian H, Burgess M, Mani DR, Lee RT, Sabatine MS, Gerszten RE, Carr SA (2009) Developing multiplexed assays for troponin I and interleukin-33 in plasma by peptide immunoaffinity enrichment and targeted mass spectrometry. Clin Chem 55:1108–1117

    Article  PubMed  CAS  Google Scholar 

  63. Whiteaker JR, Zhao L, Anderson L, Paulovich AG (2010) An automated and multiplexed method for high throughput peptide immunoaffinity enrichment and multiple reaction monitoring mass spectrometry-based quantification of protein biomarkers. Mol Cell Proteomics 9:184–196

    Article  PubMed  CAS  Google Scholar 

  64. Schoenherr RM, Zhao L, Whiteaker JR, Feng LC, Li L, Liu L, Liu X, Paulovich AG (2010) Automated screening of monoclonal antibodies for SISCAPA assays using a magnetic bead processor and liquid chromatography-selected reaction monitoring-mass spectrometry. J Immunol Methods 353:49–61

    Article  PubMed  CAS  Google Scholar 

  65. Lange V, Picotti P, Domon B, Aebersold R (2008) Selected reaction monitoring for quantitative proteomics: a tutorial. Mol Syst Biol 4:222

    Article  PubMed  Google Scholar 

  66. Picotti P, Lam H, Campbell D, Deutsch EW, Mirzaei H, Ranish J, Domon B, Aebersold R (2008) A database of mass spectrometric assays for the yeast proteome. Nat Methods 5:913–914

    Article  PubMed  CAS  Google Scholar 

  67. Picotti P, Rinner O, Stallmach R, Dautel F, Farrah T, Domon B, Wenschuh H, Aebersold R (2010) High-throughput generation of selected reaction-monitoring assays for proteins and proteomes. Nat Methods 7:43–46

    Article  PubMed  CAS  Google Scholar 

  68. Wilm M, Mann M (1996) Analytical properties of the nanoelectrospray ion source. Anal Chem 68:1–8

    Article  PubMed  CAS  Google Scholar 

  69. Craig R, Beavis RC (2004) TANDEM: matching proteins with tandem mass spectra. Bioinformatics 20:1466–1467

    Article  PubMed  CAS  Google Scholar 

  70. Colinge J, Masselot A, Giron M, Dessingy T, Magnin J (2003) OLAV: towards high-throughput tandem mass spectrometry data identification. Proteomics 3:1454–1463

    Article  PubMed  CAS  Google Scholar 

  71. Boja ES, Phillips D, French SA, Harris RA, Balaban RS (2009) Quantitative mitochondrial phosphoproteomics using iTRAQ on an LTQ-Orbitrap with high energy collision dissociation. J Proteome Res 8:4665–4675

    Article  PubMed  CAS  Google Scholar 

  72. Phanstiel D, Unwin R, McAlister GC, Coon JJ (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 

  73. Phanstiel D, Zhang Y, Marto JA, Coon JJ (2008) Peptide and protein quantification using iTRAQ with electron transfer dissociation. J Am Soc Mass Spectrom 19:1255–1262

    Article  PubMed  CAS  Google Scholar 

  74. Bantscheff M, Boesche M, Eberhard D, Matthieson T, Sweetman G, 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 

  75. Savitski MM, Fischer F, Mathieson T, Sweetman G, Lang M, Bantscheff M (2010) Targeted data acquisition for improved reproducibility and robustness of proteomic mass spectrometry assays. J Am Soc Mass Spectrom 21:1668–1679

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this protocol

Cite this protocol

Lengqvist, J., Sandberg, A. (2013). Stable Isotope Labeling Methods in Protein Profiling. In: Bäckvall, H., Lehtiö, J. (eds) The Low Molecular Weight Proteome. Methods in Molecular Biology, vol 1023. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7209-4_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7209-4_3

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-7167-7

  • Online ISBN: 978-1-4614-7209-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics