biostudies-literatureChen ZNSFNational Center for Research ResourcesNCRR NIH HHSNational Institute of General Medical SciencesNIH HHSNIGMS NIH HHS436-445https://www.ebi.ac.uk/biostudies/studies/S-EPMC9149727biostudies-literatureUnknown33(3)Glycan structure identification is essential to understanding the roles of glycans in various biological processes. Previously, we developed GlycoDeNovo, a <i>de novo</i> algorithm for reconstructing glycan topologies from tandem mass spectra (MS/MS). In this work, we introduce GlycoDeNovo2 that contains two major improvements to GlycoDeNovo. First, we use the precursor mass measured for a peak that likely corresponds to a glycan to determine its potential compositions, which are used to constrain the search space, enable parallel computation, and hence speed up topology reconstruction. Second, we developed a procedure to calculate the empirical <i>p</i>-value of a reconstructed topology candidate. Experimental results are provided to demonstrate the effectiveness of GlycoDeNovo2.Journal of the American Society for Mass SpectrometryGlycoDeNovo2: An Improved MS/MS-Based <i>De Novo</i> Glycan Topology Reconstruction Algorithm.PMC9149727NIH R24 GM134210R24 GM134210S10 RR025082S10 OD021728NIH R01 GM132675R01 GM132675NIH S10 RR025082NSF OAC 1920147Lin CChen ZCostello CEWei JHong PTang YfalseGlycoDeNovo2: An Improved MS/MS-Based <i>De Novo</i> Glycan Topology Reconstruction Algorithm.Glycan structure identification is essential to understanding the roles of glycans in various biological processes. Previously, we developed GlycoDeNovo, a <i>de novo</i> algorithm for reconstructing glycan topologies from tandem mass spectra (MS/MS). In this work, we introduce GlycoDeNovo2 that contains two major improvements to GlycoDeNovo. First, we use the precursor mass measured for a peak that likely corresponds to a glycan to determine its potential compositions, which are used to constrain the search space, enable parallel computation, and hence speed up topology reconstruction. Second, we developed a procedure to calculate the empirical <i>p</i>-value of a reconstructed topology candidate. Experimental results are provided to demonstrate the effectiveness of GlycoDeNovo2.2022-01-01T00:00:00Z2022 Mar2025-04-05T14:19:55.16Z2025-04-05T14:19:55.16ZS-EPMC91497273515745810.1021/jasms.1c00288