UniCarbKB: building a knowledge platform for glycoproteomics

Abstract

The UniCarb KnowledgeBase (UniCarbKB; http://unicarbkb.org) offers public access to a growing, curated database of information on the glycan structures of glycoproteins. UniCarbKB is an international effort that aims to further our understanding of structures, pathways and networks involved in glycosylation and glyco-mediated processes by integrating structural, experimental and functional glycoscience information. This initiative builds upon the success of the glycan structure database GlycoSuiteDB, together with the informatic standards introduced by EUROCarbDB, to provide a high-quality and updated resource to support glycomics and glycoproteomics research. UniCarbKB provides comprehensive information concerning glycan structures, and published glycoprotein information including global and site-specific attachment information. For the first release over 890 references, 3740 glycan structure entries and 400 glycoproteins have been curated. Further, 598 protein glycosylation sites have been annotated with experimentally confirmed glycan structures from the literature. Among these are 35 glycoproteins, 502 structures and 60 publications previously not included in GlycoSuiteDB. This article provides an update on the transformation of GlycoSuiteDB (featured in previous NAR Database issues and hosted by ExPASy since 2009) to UniCarbKB and its integration with UniProtKB and GlycoMod. Here, we introduce a refactored database, supported by substantial new curated data collections and intuitive user-interfaces that improve database searching.

Strategies for carbohydrate model building, refinement and validation

“…Additionally, thanks to the GlycanBuilder graphical software (Damerell et al, 2012(Damerell et al, , 2015, it is possible to interrogate massspectrometry databases such as UniCarbKB (Campbell et al, 2014) and more recently glycosciences.de (Loss & Lü tteke, 2015;Lü tteke et al, 2006) using the familiar Essentials nomenclature to browse for experimental evidence of the occurrence of a particular glycan in a particular expression system. N-glycan structures have been reviewed in detail in .…”

“…While Privateer (Agirre, Iglesias-Ferná ndez et al, 2015) and PDB-CARE (Lü tteke & von der Lieth, 2004) will cross-check input structures against the common characteristics of glycans based on the expression system used, it is worth using a database such as UniCarbKB (Campbell et al, 2014) or glycosciences.de (Loss & Lü tteke, 2015;Lü tteke et al, 2006) through GlycanBuilder (Damerell et al, 2012(Damerell et al, , 2015 to obtain experimental confirmation for longer or more complex glycans. A recent summary of the available tools has been published by Emsley et al (2015).…”

Radical mediated dissection of oligosaccharides

“…This limitation can be mitigated by building a reference library of spectra for comparison against an unknown analyte. Various methods have been used to collect characteristic tandem MS spectra for disaccharides, and it has been found that generally the more fragments that are generated the higher the probability of identifying the unknown species [25,26]. Due to these constraints, CID of protonated disaccharides is not effective because most fragments come from glycoside bond cleavage.…”

Integrative methods for analyzing big data in precision medicine

“…Link Content NCBI Gene [66] www.ncbi.nlm.nih.gov/gene Atlas of 59,500 human genes GOA [67] www.ebi.ac.uk/GOA 487,409 Gene Ontology annotations for 48,569 human gene products ENCODE [68] www.encodeproject.org Functional annotations of coding/non-coding DNA elements NCBI Epigenomics [69] www.ncbi.nlm.nih.gov/epigenomics 5,110 epigenetic modifications 4DGenome [70] 4dgenome [73] www.ebi.ac.uk/gxa Differential and baseline gene expression data CMAP [74] www.broadinstitute.org/cmap ∼ 7,000 expression profiles for 1,309 perturbagen compounds COXPRESdb [75] coxpresdb.jp Co-expression of 19,803 human genes GeneFriends [76] genefriends.org Co-expression of 159,184 human genes and transcripts UniProt [77] www.uniprot.org Information about human proteome (69,693 proteins) NeXtProt [78] www.nextprot.org Knowledgebase on 20,066 human proteins RCSB PDB [79] www.rcsb.org/pdb Portal to 113,494 biological macromolecular 3D-structures HPA [80] www.thehpp.org Maps of human proteome on 44 normal and 20 cancer type tissues IntAct [81] www.ebi.ac.uk/intact 209,852 human protein-protein interactions BioGrid [82] thebiogrid.org 215,952 human protein-protein interactions I2D [83] ophid.utoronto.ca 183,524 (+ 55,985 predicted) protein-protein interactions STRING [84] string-db.org 8,548,005 interactions between 20,457 proteins HMDB [85] www.hmdb.ca Atlas of 41,993 human metabolites KEGG Pathway [86] www.genome.jp/kegg/pathway 298 human pathways SMPD [87] www.smpdb.ca ∼700 human metabolic and disease pathways Reactome [88] www.reactome.org 8,770 reactions in 1,887 human pathways SugarBindDB [89] sugarbind.expasy.org 1,256 interactions between 200 glycans and 551 pathogenic agents UniCarbKB [90] www.unicarbkb.org 3,740 glycan structure entries and 400 glycoproteins KEGG Glycan [91] www.genome.jp/kegg/glycan/ Glycan metabolic pathways OMIM [92] www.omim.org Catalog of mendelian disorders and over 15,000 genes NCBI dbGaP [93] www.ncbi.nlm.nih.gov/gap Database of genotypes and phenotypes GWAS Catalog [94] www.ebi.ac.uk/gwas/ Genome wide association studies, assaying ∼ 100,000 SNPs COSMIC...…”