GlycoPep grader: a web-based utility for assigning the composition of N-linked glycopeptides.

GlycoPep grader (GPG) is a freely available software tool designed to accelerate the process of accurately determining glycopeptide composition from tandem mass spectrometric data. GPG relies on the identification of unique dissociation patterns shown for high mannose, hybrid, and complex N-linked glycoprotein types, including patterns specific to those structures containing fucose or sialic acid residues. The novel GPG scoring algorithm scores potential candidate compositions of the same nominal mass against MS/MS data through evaluation of the Y(1) ion and other peptide-containing product ions, across multiple charge states, when applicable. In addition to evaluating the peptide portion of a given glycopeptide, the GPG algorithm predicts and scores product ions that result from unique neutral losses of terminal glycans. GPG has been applied to a variety of glycoproteins, including RNase B, asialofetuin, and transferrin, and the HIV envelope glycoprotein, CON-S gp140ΔCFI. The GPG software is implemented predominantly in PostgreSQL, with PHP as the presentation tier, and is publicly accessible online. Thus far, the algorithm has identified the correct compositional assignment from multiple candidate N-glycopeptides in all tests performed.

[1]  D. Seligson,et al.  Clinical Chemistry , 1965, Bulletin de la Societe de chimie biologique.

[2]  R Apweiler,et al.  On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. , 1999, Biochimica et biophysica acta.

[3]  G A Petsko,et al.  Chemistry and biology. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Carolyn R. Bertozzi,et al.  Chemical Glycobiology , 2001, Science.

[5]  A. Helenius,et al.  Intracellular functions of N-linked glycans. , 2001, Science.

[6]  Catherine A. Cooper,et al.  GlycoMod – A software tool for determining glycosylation compositions from mass spectrometric data , 2001, Proteomics.

[7]  Michael J Deery,et al.  Precursor ion scanning for detection and structural characterization of heterogeneous glycopeptide mixtures , 2002, Journal of the American Society for Mass Spectrometry.

[8]  A. Levchenko,et al.  The Systems Biology of Glycosylation , 2004, Chembiochem : a European journal of chemical biology.

[9]  T. Takao,et al.  Site-specific carbohydrate profiling of human transferrin by nano-flow liquid chromatography/electrospray ionization mass spectrometry. , 2004, Rapid communications in mass spectrometry : RCM.

[10]  André M Deelder,et al.  Protein glycosylation analysis by liquid chromatography-mass spectrometry. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[11]  J. Michalski,et al.  The use of mass spectrometry for the proteomic analysis of glycosylation , 2006, Proteomics.

[12]  Richard S. Lee,et al.  Global methods for protein glycosylation analysis by mass spectrometry. , 2006, Biochimica et biophysica acta.

[13]  Raymond A Dwek,et al.  Structural aspects of glycomes with a focus on N-glycosylation and glycoprotein folding. , 2006, Current opinion in structural biology.

[14]  André M Deelder,et al.  Glycoproteomics based on tandem mass spectrometry of glycopeptides. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[15]  David Goldberg,et al.  Automated N-glycopeptide identification using a combination of single- and tandem-MS. , 2007, Journal of proteome research.

[16]  E. Go,et al.  GlycoPep DB: a tool for glycopeptide analysis using a "Smart Search". , 2007, Analytical chemistry.

[17]  E. Go,et al.  Simplification of mass spectral analysis of acidic glycopeptides using GlycoPep ID. , 2007, Analytical chemistry.

[18]  Jian Min Ren,et al.  N-Glycan structure annotation of glycopeptides using a linearized glycan structure database (GlyDB). , 2007, Journal of proteome research.

[19]  René Ranzinger,et al.  “Glyco‐peakfinder” – de novo composition analysis of glycoconjugates , 2007, Proteomics.

[20]  Bin Ma,et al.  Complexities and Algorithms for Glycan Sequencing Using Tandem Mass Spectrometry , 2008, J. Bioinform. Comput. Biol..

[21]  Alessio Ceroni,et al.  GlycoWorkbench: a tool for the computer-assisted annotation of mass spectra of glycans. , 2008, Journal of proteome research.

[22]  Joseph Zaia,et al.  Mass spectrometry and the emerging field of glycomics. , 2008, Chemistry & biology.

[23]  E. Go,et al.  Glycosylation site-specific analysis of HIV envelope proteins (JR-FL and CON-S) reveals major differences in glycosylation site occupancy, glycoform profiles, and antigenic epitopes' accessibility. , 2008, Journal of proteome research.

[24]  Eric D. Dodds,et al.  Factors that influence fragmentation behavior of N-linked glycopeptide ions. , 2008, Analytical chemistry.

[25]  H. Desaire,et al.  Glycopeptide analysis by mass spectrometry. , 2008, The Analyst.

[26]  Sakari Joenväärä,et al.  N-glycoproteomics - an automated workflow approach. , 2008, Glycobiology.

[27]  László Drahos,et al.  GlycoMiner: a new software tool to elucidate glycopeptide composition. , 2008, Rapid communications in mass spectrometry : RCM.

[28]  W. Alley,et al.  Characterization of glycopeptides by combining collision-induced dissociation and electron-transfer dissociation mass spectrometry data. , 2009, Rapid communications in mass spectrometry : RCM.

[29]  E. Go,et al.  Label-free quantitation: A new glycoproteomics approach , 2009, Journal of the American Society for Mass Spectrometry.

[30]  R. Renkonen,et al.  De novo glycan structure search with the CID MS/MS spectra of native N-glycopeptides. , 2009, Glycobiology.

[31]  Danielle Skropeta,et al.  The effect of individual N-glycans on enzyme activity. , 2009, Bioorganic & medicinal chemistry.

[32]  H. Desaire,et al.  When can glycopeptides be assigned based solely on high-resolution mass spectrometry data? , 2009 .

[33]  Susan J Fisher,et al.  Sweetening the pot: adding glycosylation to the biomarker discovery equation. , 2010, Clinical chemistry.

[34]  Zhongqi Zhang,et al.  Prediction of collision-induced dissociation spectra of common N-glycopeptides for glycoform identification. , 2010, Analytical chemistry.

[35]  B. Garcia,et al.  Proteomics , 2011, Journal of biomedicine & biotechnology.

[36]  M. Emmett,et al.  Liquid chromatography electrospray ionization Fourier transform ion cyclotron resonance mass spectrometric characterization of N-linked glycans and glycopeptides. , 2010, Analytical chemistry.

[37]  Angela M Zivkovic,et al.  Simultaneous and extensive site-specific N- and O-glycosylation analysis in protein mixtures. , 2011, Journal of proteome research.