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Journal of The American Society for Mass Spectrometry

, Volume 29, Issue 9, pp 1802–1811 | Cite as

An Automated, High-Throughput Method for Interpreting the Tandem Mass Spectra of Glycosaminoglycans

  • Jiana Duan
  • I. Jonathan Amster
Focus: Application of Photons and Radicals for MS: Research Article

Abstract

The biological interactions between glycosaminoglycans (GAGs) and other biomolecules are heavily influenced by structural features of the glycan. The structure of GAGs can be assigned using tandem mass spectrometry (MS2), but analysis of these data, to date, requires manually interpretation, a slow process that presents a bottleneck to the broader deployment of this approach to solving biologically relevant problems. Automated interpretation remains a challenge, as GAG biosynthesis is not template-driven, and therefore, one cannot predict structures from genomic data, as is done with proteins. The lack of a structure database, a consequence of the non-template biosynthesis, requires a de novo approach to interpretation of the mass spectral data. We propose a model for rapid, high-throughput GAG analysis by using an approach in which candidate structures are scored for the likelihood that they would produce the features observed in the mass spectrum. To make this approach tractable, a genetic algorithm is used to greatly reduce the search-space of isomeric structures that are considered. The time required for analysis is significantly reduced compared to an approach in which every possible isomer is considered and scored. The model is coded in a software package using the MATLAB environment. This approach was tested on tandem mass spectrometry data for long-chain, moderately sulfated chondroitin sulfate oligomers that were derived from the proteoglycan bikunin. The bikunin data was previously interpreted manually. Our approach examines glycosidic fragments to localize SO3 modifications to specific residues and yields the same structures reported in literature, only much more quickly.

Graphical Abstract

Keywords

Glycosaminoglycan Fourier transform mass spectrometry Tandem mass spectrometry Automated interpretation 

References

  1. 1.
    Xie, B., Costello, C.E.: Carbohydrate structure determination by mass spectrometry. Carbohydr. Chem. Biol. Med. Appl. 29–57 (2008)Google Scholar
  2. 2.
    Gandhi, N.S., Mancera, R.L.: The structure of glycosaminoglycans and their interactions with proteins. Chem. Biol. Drug Des. 72, 455–482 (2008)CrossRefPubMedGoogle Scholar
  3. 3.
    Rabenstein, D.L.: Heparin and heparan sulfate: structure and function. Nat. Prod. Rep. 19, 312–331 (2002)CrossRefPubMedGoogle Scholar
  4. 4.
    Ohtsubo, K., Marth, J.D.: Glycosylation in cellular mechanisms of health and disease. Cell. 126, 855–867 (2006)CrossRefPubMedGoogle Scholar
  5. 5.
    Zhao, Y.J., Singh, A., Li, L.Y., Linhardt, R.J., Xu, Y.M., Liu, J., Woods, R.J., Amster, I.J.: Investigating changes in the gas-phase conformation of Antithrombin III upon binding of Arixtra using traveling wave ion mobility spectrometry (TWIMS). Analyst. 14, 6980–6989 (2015)CrossRefGoogle Scholar
  6. 6.
    Zhao, Y.J., Singh, A., Xu, Y.M., Zong, C.L., Zhang, F.M., Boons, G.J., Liu, J., Linhardt, R.J., Woods, R.J., Amster, I.J.: Gas-phase analysis of the complex of fibroblast growth factor 1 with heparan sulfate: a traveling wave ion mobility spectrometry (TWIMS) and molecular modeling study. J. Am. Soc. Mass Spectrom. 28, 96–109 (2017)CrossRefPubMedGoogle Scholar
  7. 7.
    Thanawiroon, C., Rice, K.G., Toida, T., Linhardt, R.J.: Liquid chromatography/mass spectrometry sequencing approach for highly sulfated heparin-derived oligosaccharides. J. Biol. Chem. 279, 2608–2615 (2004)CrossRefPubMedGoogle Scholar
  8. 8.
    Jones, C.J., Beni, S., Limtiaco, J.F.K., Langeslay, D.J., Larive, C.K.: Heparin characterization: challenges and solutions. Annu. Rev. Anal. Chem. 4(4), 439–465 (2011)CrossRefGoogle Scholar
  9. 9.
    Elias, J.E., Haas, W., Faherty, B.K., Gygi, S.P.: Comparative evaluation of mass spectrometry platforms used in large-scale proteomics investigations. Nat. Methods. 2, 667–675 (2005)CrossRefPubMedGoogle Scholar
  10. 10.
    Cox, J., Neuhauser, N., Michalski, A., Scheltema, R.A., Olsen, J.V., Mann, M.: Andromeda: a peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 10, 1794–1805 (2011)CrossRefPubMedGoogle Scholar
  11. 11.
    Chi, L.L., Amster, J., Linhardt, R.J.: Mass spectrometry for the analysis of highly charged sulfated carbohydrates. Curr. Anal. Chem. 1, 223–240 (2005)CrossRefGoogle Scholar
  12. 12.
    Cooper, C.A., Gasteiger, E., Packer, N.H.: GlycoMod—a software tool for determining glycosylation compositions from mass spectrometric data. Proteomics. 1, 340–349 (2001)CrossRefPubMedGoogle Scholar
  13. 13.
    Kailemia, M.J., Patel, A.B., Johnson, D.T., Li, L.Y., Linhardt, R.J., Amster, I.J.: Differentiating chondroitin sulfate glycosaminoglycans using collision-induced dissociation; uronic acid cross-ring diagnostic fragments in a single stage of tandem mass spectrometry. Eur. J. Mass Spectrom. 21, 275–285 (2015)CrossRefGoogle Scholar
  14. 14.
    Flangea, C., Serb, A.F., Schiopu, C., Tudor, S., Sisu, E., Seidler, D.G., Zamfir, A.D.: Discrimination of GalNAc (4S/6S) sulfation sites in chondroitin sulfate disaccharides by chip-based nanoelectrospray multistage mass spectrometry. Cent. Eur. J. Chem. 7, 752–759 (2009)Google Scholar
  15. 15.
    Huang, R.R., Pomin, V.H., Sharp, J.S.: LC-MS (n) analysis of isomeric chondroitin sulfate oligosaccharides using a chemical derivatization strategy. J. Am. Soc. Mass Spectrom. 22, 1577–1587 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Leach, F.E., Xiao, Z.P., Laremore, T.N., Linhardt, R.J., Amster, I.J.: Electron detachment dissociation and infrared multiphoton dissociation of heparin tetrasaccharides. Int. J. Mass Spectrom. 308, 253–259 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bin Oh, H., Leach, F.E., Arungundram, S., Al-Mafraji, K., Venot, A., Boons, G.J., Amster, I.J.: Multivariate analysis of electron detachment dissociation and infrared multiphoton dissociation mass spectra of heparan sulfate tetrasaccharides differing only in hexuronic acid stereochemistry. J. Am. Soc. Mass Spectrom. 22, 582–590 (2011)CrossRefGoogle Scholar
  18. 18.
    Wolff, J.J., Laremore, T.N., Leach, F.E., Linhardt, R.J., Amster, I.J.: Electron capture dissociation, electron detachment dissociation and infrared multiphoton dissociation of sucrose octasulfate. Eur. J. Mass Spectrom. 15, 275–281 (2009)CrossRefGoogle Scholar
  19. 19.
    Wolff, J.J., Laremore, T.N., Busch, A.M., Linhardt, R.J., Amster, I.J.: Influence of charge state and sodium cationization on the electron detachment dissociation and infrared multiphoton dissociation of glycosaminoglycan oligosaccharides. J. Am. Soc. Mass Spectrom. 19, 790–798 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Leach, F.E., Ly, M., Laremore, T.N., Wolff, J.J., Perlow, J., Linhardt, R.J., Amster, I.J.: Hexuronic acid stereochemistry determination in chondroitin sulfate glycosaminoglycan oligosaccharides by electron detachment dissociation. J. Am. Soc. Mass Spectrom. 23, 1488–1497 (2012)CrossRefPubMedGoogle Scholar
  21. 21.
    Leach, F.E., Wolff, J.J., Laremore, T.N., Linhardt, R.J., Amster, I.J.: Evaluation of the experimental parameters which control electron detachment dissociation, and their effect on the fragmentation efficiency of glycosaminoglycan carbohydrates. Int. J. Mass Spectrom. 276, 110–115 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wolff, J.J., Chi, L.L., Linhardt, R.J., Amster, I.J.: Distinguishing glucuronic from iduronic acid in glycosaminoglycan tetrasaccharides by using electron detachment dissociation. Anal. Chem. 79, 2015–2022 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Wolff, J.J., Laremore, T.N., Aslam, H., Linhardt, R.J., Amster, I.J.: Electron-induced dissociation of glycosaminoglycan tetrasaccharides. J. Am. Soc. Mass Spectrom. 19, 1449–1458 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Wolff, J.J., Laremore, T.N., Busch, A.M., Linhardt, R.J., Amster, I.J.: Electron detachment dissociation of dermatan sulfate oligosaccharides. J. Am. Soc. Mass Spectrom. 19, 294–304 (2008)CrossRefPubMedGoogle Scholar
  25. 25.
    Huang, Y., Yu, X., Mao, Y., Costello, C.E., Zaia, J., Lin, C.: De novo sequencing of heparan sulfate oligosaccharides by electron-activated dissociation. Anal. Chem. 85, 11979–11986 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Leach, F.E., Riley, N.M., Westphall, M.S., Coon, J.J., Amster, I.J.: Negative electron transfer dissociation sequencing of increasingly sulfated glycosaminoglycan oligosaccharides on an orbitrap mass spectrometer. J. Am. Soc. Mass Spectrom. 28, 1844–1854 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Wolff, J.J., Leach, F.E., Laremore, T.N., Kaplan, D.A., Easterling, M.L., Linhardt, R.J., Amster, I.J.: Negative electron transfer dissociation of glycosaminoglycans. Anal. Chem. 82, 3460–3466 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wolff, J.J., Amster, I.J., Chi, L., Linhardt, R.J.: Electron detachment dissociation of glycosaminoglycan tetrasaccharides. J. Am. Soc. Mass Spectrom. 18, 234–244 (2007)CrossRefPubMedGoogle Scholar
  29. 29.
    Domon, B., Costello, C.E.: A systematic nomenclature for carbohydrate fragmentations in fab-ms ms spectra of glycoconjugates. Glycoconjugate J. 5, 397–409 (1988)CrossRefGoogle Scholar
  30. 30.
    Kailemia, M.J., Li, L.Y., Ly, M., Linhardt, R.J., Amster, I.J.: Complete mass spectral characterization of a synthetic ultralow-molecular-weight heparin using collision-induced dissociation. Anal. Chem. 84, 5475–5478 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kailemia, M.J., Ruhaak, L.R., Lebrilla, C.B., Amster, I.J.: Oligosaccharide analysis by mass spectrometry: a review of recent developments. Anal. Chem. 86, 196–212 (2014)CrossRefPubMedGoogle Scholar
  32. 32.
    Zaia, J., Costello, C.E.: Tandem mass spectrometry of sulfated heparin-like glycosaminoglycan oligosaccharides. Anal. Chem. 75, 2445–2455 (2003)CrossRefPubMedGoogle Scholar
  33. 33.
    Dancik, V., Addona, T.A., Clauser, K.R., Vath, J.E., Pevzner, P.A.: De novo peptide sequencing via tandem mass spectrometry. J. Comput. Biol. 6, 327–342 (1999)CrossRefPubMedGoogle Scholar
  34. 34.
    Ma, B., Zhang, K.Z., Hendrie, C., Liang, C.Z., Li, M., Doherty-Kirby, A., Lajoie, G.: PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry. Rapid Commun. Mass Spectrom. 17, 2337–2342 (2003)CrossRefPubMedGoogle Scholar
  35. 35.
    Taylor, J.A., Johnson, R.S.: Implementation and uses of automated de novo peptide sequencing by tandem mass spectrometry. Anal. Chem. 73, 2594–2604 (2001)CrossRefPubMedGoogle Scholar
  36. 36.
    Campbell, M.P., Hayes, C.A., Struwe, W.B., Wilkins, M.R., Aoki-Kinoshita, K.F., Harvey, D.J., Rudd, P.M., Kolarich, D., Lisacek, F., Karlsson, N.G., Packer, N.H.: UniCarbKB: putting the pieces together for glycomics research. Proteomics. 11, 4117–4121 (2011)CrossRefPubMedGoogle Scholar
  37. 37.
    Maxwell, E., Tan, Y., Tan, Y., Hu, H., Benson, G., Aizikov, K., Conley, S., Staples, G.O., Slysz, G.W., Smith, R.D., Zaia, J.: GlycReSoft: a software package for automated recognition of glycans from LC/MS data. PLoS One. 7, (2012)Google Scholar
  38. 38.
    Saad, O.M., Leary, J.A.: Heparin sequencing using enzymatic digestion and ESI-MSn with HOST: a heparin/HS oligosaccharide sequencing tool. Anal. Chem. 77, 5902–5911 (2005)CrossRefPubMedGoogle Scholar
  39. 39.
    Chiu, Y.L., Huang, R.R., Orlando, R., Sharp, J.S.: GAG-ID: heparan sulfate (HS) and heparin glycosaminoglycan high-throughput identification software. Mol. Cell. Proteomics. 14, 1720–1730 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hu, H., Huang, Y., Mao, Y., Yu, X., Xu, Y.M., Liu, J., Zong, C.L., Boons, G.J., Lin, C., Xia, Y., Zaia, J.: A computational framework for heparan sulfate sequencing using high-resolution tandem mass spectra. Mol. Cell. Proteomics. 13, 2490–2502 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ly, M., Leach III, F.E., Laremore, T.N., Toida, T., Amster, I.J., Linhardt, R.J.: The proteoglycan bikunin has a defined sequence. Nat. Chem. Biol. 7, 827–833 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Baeck, T., Schwefel, H.-P.: An overview of evolutionary algorithms for parameter optimization. Evol. Comput. 1, 1–23 (1993)CrossRefGoogle Scholar
  43. 43.
    Fogel, L.J., Owens, A.J., Walsh, M.J.: Artificial intelligence through a simulation of evolution. Proceedings of the Second Cybernetic Sciences Symposium: Biophysics and cybernetic systems. 131–155 (1965)Google Scholar
  44. 44.
    Forrest, S.: Genetic algorithms—principles of natural-selection applied to computation. Science. 261, 872–878 (1993)CrossRefPubMedGoogle Scholar
  45. 45.
    Han, L., Costello, C.E.: Mass spectrometry of glycans. Biochem. Mosc. 78, 710–720 (2013)CrossRefGoogle Scholar
  46. 46.
    Kilgour, D.P.A., Neal, M.J., Soulby, A.J., O’Connor, P.B.: Improved optimization of the Fourier transform ion cyclotron resonance mass spectrometry phase correction function using a genetic algorithm. Rapid Commun. Mass Spectrom. 27, 1977–1982 (2013)CrossRefPubMedGoogle Scholar
  47. 47.
    Das, S., Suganthan, P.N.: Differential evolution: a survey of the state-of-the-art. IEEE Trans. Evol. Comput. 15, 4–31 (2011)CrossRefGoogle Scholar
  48. 48.
    Knowles, J.D., Corne, D.W.: Approximating the nondominated front using the Pareto archived evolution strategy. Evol. Comput. 8, 149–172 (2000)CrossRefPubMedGoogle Scholar
  49. 49.
    Phillips, S.J., Anderson, R.P., Schapire, R.E.: Maximum entropy modeling of species geographic distributions. Ecol. Model. 190, 231–259 (2006)CrossRefGoogle Scholar
  50. 50.
    Tavazoie, S., Hughes, J.D., Campbell, M.J., Cho, R.J., Church, G.M.: Systematic determination of genetic network architecture. Nat. Genet. 22, 281–285 (1999)CrossRefPubMedGoogle Scholar
  51. 51.
    Verdonk, M.L., Cole, J.C., Hartshorn, M.J., Murray, C.W., Taylor, R.D.: Improved protein-ligand docking using GOLD. Proteins Struct. Funct. Genet. 52, 609–623 (2003)CrossRefPubMedGoogle Scholar
  52. 52.
    Yu, Y.L., Duan, J.N., Leach, F.E., Toida, T., Higashi, K., Zhang, H., Zhang, F.M., Amster, I.J., Linhardt, R.J.: Sequencing the dermatan sulfate chain of decorin. J. Am. Chem. Soc. 139, 16986–16995 (2017)CrossRefPubMedGoogle Scholar
  53. 53.
    Singh, A., Kett, W.C., Severin, I.C., Agyekum, I., Duan, J.N., Amster, I.J., Proudfoot, A.E.I., Coombe, D.R., Woods, R.J.: The interaction of heparin tetrasaccharides with chemokine CCL5 is modulated by sulfation pattern and pH. J. Biol. Chem. 290, 15421–15436 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Agyekum, I., Patel, A.B., Zong, C.L., Boons, G.J., Amster, I.J.: Assignment of hexuronic acid stereochemistry in synthetic heparan sulfate tetrasaccharides with 2-O-sulfo uronic acids using electron detachment dissociation. Int. J. Mass Spectrom. 390, 163–169 (2015)CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of GeorgiaAthensUSA

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