title: A computational framework for heparan sulfate sequencing using high-resolution tandem mass spectra.
abstract: Heparan sulfate (HS) is a linear polysaccharide expressed on cell surfaces, in extracellular matrices and cellular granules in metazoan cells. Through non-covalent binding to growth factors, morphogens, chemokines, and other protein families, HS is involved in all multicellular physiological activities. Its biological activities depend on the fine structures of its protein-binding domains, the determination of which remains a daunting task. Methods have advanced to the point that mass spectra with information-rich product ions may be produced on purified HS saccharides. However, the interpretation of these complex product ion patterns has emerged as the bottleneck to the dissemination of these HS sequencing methods. To solve this problem, we designed HS-SEQ, the first comprehensive algorithm for HS de novo sequencing using high-resolution tandem mass spectra. We tested HS-SEQ using negative electron transfer dissociation (NETD) tandem mass spectra generated from a set of pure synthetic saccharide standards with diverse sulfation patterns. The results showed that HS-SEQ rapidly and accurately determined the correct HS structures from large candidate pools.
authors.affiliation: From the ‡Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA; §Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, Massachusetts 02118, USA;
authors.forename: Han
authors.initials: H
authors.lastname: Hu
authors.affiliation: §Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, Massachusetts 02118, USA;
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: §Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, Massachusetts 02118, USA;
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: §Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, Massachusetts 02118, USA;
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.affiliation: ¶ Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: ¶ Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA;
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: **Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602.
authors.forename: Chengli
authors.initials: C
authors.lastname: Zong
authors.affiliation: **Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602.
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
authors.affiliation: §Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, Massachusetts 02118, USA;
authors.forename: Cheng
authors.initials: C
authors.lastname: Lin
authors.affiliation: ‖Department of Bioengineering, Faculty of Engineering, McGill University, Montreal, Quebec H3A 0C3, Canada; From the ‡Bioinformatics Program, Boston University, Boston, Massachusetts 02215, USA;
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.affiliation: §Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, Massachusetts 02118, USA; jzaia@bu.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zaia
mesh_terms: D000465:Algorithms; D002240:Carbohydrate Sequence; D006497:Heparan Sulfate / Q000737:chemistry*; D017421:Sequence Analysis / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D006497:Heparan Sulfate