GlycoCD: a repository for carbohydrate-related CD antigens

Bioinformatics, Oct 2012

Summary: The open access comprehensive GlycoCD database application is for representation and retrieval of carbohydrate-related clusters of differentiation (CDs). The main objective of this database platform is to provide information about interactions of carbohydrate moieties with proteins that are important for identification of specific cell surface molecule with a focus on the integration of data from carbohydrate microarray databases. GlycoCD database comprises two sections: the carbohydrate recognition CD and glycan CD. It allows easy access through a user-friendly web interface to all carbohydrate-defined CDs and those that interact with carbohydrates along with other relevant information. Availability: The database is freely available at http://glycosciences.de/glycocd/index.php Contact: r.s-albiez{at}dkfz.de

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GlycoCD: a repository for carbohydrate-related CD antigens

Sonu Kumar 1 Thomas L utteke 0 Reinhard Schwartz-Albiez 1 Associate Editor: Janet Kelso 0 Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen , D-35392 Giessen , Germany 1 D015, Translational Immunology, German Cancer Research Center , INF 280, D-69120 Heidelberg Summary: The open access comprehensive GlycoCD database application is for representation and retrieval of carbohydrate-related clusters of differentiation (CDs). The main objective of this database platform is to provide information about interactions of carbohydrate moieties with proteins that are important for identification of specific cell surface molecule with a focus on the integration of data from carbohydrate microarray databases. GlycoCD database comprises two sections: the carbohydrate recognition CD and glycan CD. It allows easy access through a user-friendly web interface to all carbohydrate-defined CDs and those that interact with carbohydrates along with other relevant information. Availability: The database is freely available at http://glycosciences .de/glycocd/index.php Contact: The Author 2012. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: - Received on April 2, 2012; revised on July 24, 2012; accepted on July 25, 2012 1 INTRODUCTION The clusters of differentiation (CD) antigens are cell surfaceexpressed antigens defined by monoclonal antibodies. The great value of the CD nomenclature, validated and approved as part of the International Union of Immunological Societies nomenclature (Zola et al., 2003), is to provide a unified system of classified antigens useful both for biomedical research and clinical practice. The CD antibodies have been categorized during the past 28 years in Human Leucocyte Differentiation Antigens (HLDA) workshops (Heddy Zola, 2007; Mason et al., 2002). The CD antigens are expressed on human hematopoietic cells (T and B lymphocytes, natural killer cells, myeloid cells, erythrocytes and platelets), specific types of endothelial and epithelial cells. The information for CD antigens expands from cellular and tissue expression to biochemical structure, genetic background and to its functional impact in a given cellular environment. The interactions of the immune system are mediated by cell surface glycoproteins and glycolipids (Schwartz-Albiez, 2009). Most of the CD antibodies recognize the protein moiety of surface, membrane integral macromolecules, but some of them detect oligosaccharide structures that are linked to either glycoproteins or glycosphingolipids. During the HLDA conference 2000, a separate workshop on carbohydrate and lectin CDs was established considering the increasing interest and advance in research in unraveling cellular *To whom correspondence should be addressed. proteinglycan interactions (Schwartz-Albiez, 2002). The objective was to initiate a more comprehensive compilation of monoclonal antibody-defined carbohydrate structures and lectins differentially expressed on human leucocytes and to provide an appropriate classification within the CD nomenclature. Some carbohydrate CD antibodies were re-organized into subgroups of CDs because of their reactivity with variations of certain oligosaccharide structures. For example, CD15 (blood group Lewis x, Lex) received additional subgroups of CD15s (sialyl Lewis x), CD15u (3sulfo Lewis x) and CD15su (6 sulfo-sialyl Lewis x). CD60 was subdivided into CD60a (the oligosaccharide structure of the disialo-ganglioside GD3 and related glycans), CD60b (9-O-acetylated sialic acid GD3) and CD60c (7-O-acetylated sialic acid GD3). CD75 comprises lactosaminyl sequences into CD75 (non-sialylated lactosamines) and CD75s (sialylated lactosamines) (Mandal, et al. 2012). The oligosaccharides of the CD75s subgroup have a different functional impact as modulators of adhesion to certain lectins such as Siglecs (Cao et al., 2008). Due to the high complexity of oligosaccharide structures, antibodies of a particular carbohydrate CD may bind to variations of the same oligosaccharide type and consequently display different cellular staining patterns. For instance, this may be due to variations in the linkage of the terminal sialic acid ( 2-6 versus 2-3), to oligosaccharide chains which extend the glycan epitope (glycotope) recognized by the respective antibody or by varying expression of the glycotope on different glycosphingolipids and/or glycoproteins on a specific cell type. In general, most carbohydrate CDs define histo-blood group antigens, which are characterized either by their different fucosylation or sialylation. This GlycoCD database now endeavours to provide in-depth information about glycan CD antigens and those CD-defined surface receptors (lectins), which bind to glycan structures. GlycoCD is a web-based, platform-independent, manually curated database. All data were collected by comprehensively searching literature, online resources and books. It has been designed as a relational database and currently runs on an Apache server. This database has been implemented using the open source MySQL database (http://www.mysql.com) that serves as the back-end for storing all the carbohydrate-related CD information along with related publications. PHP: Hypertext Preprocessor was used to fetch data from the database, while both PHP and HTML were used to make the web interface. The schematic overview is provided in Fig. 1. The database is presently hosted on a server at glycoscience.dea glycoinformatics web portaland it will be manually updated and maintained. Fig. 1. The schematic overview of GlycoCD database RESULTS AND DISCUSSION GlycoCD is a collection of lectins and carbohydrates defined by CD antibodies that are differentially expressed primarily on human leukocytes and also on certain endothelial and epithelial cells. The database comprises information on 63 CD antigens (out of 363 of total CD antigens as defined in the HLDA 9 workshop). We have categorized these data within GlycoCD repository into two sections: carbohydrate recognition CD antigens and glycan CDs. For the convenience of the user, glycan-related CDs can be searched either by the respective CD number or the glycan-binding specificity. There is a tutorial section describing the workflow in a simple manner with relevant information about the respective CD. There are online resources available which touch selective fields of CD: http://www.immu nologylink.com/cdantigen.html summarizes in short form information about CD antigens/antibodies; http://pathologyoutlines .com/cdmarkers.html provides information about the immunohistology of selected CDs and two databases: SugarBindDB (http://sugarbind.expasy.org/sugarbind/) describes carbohydratebinding proteins in the field of microbiology and GlycoEpitope (http://www.glyco.is.ritsumei.ac.jp/epitope/) for carbohydrate epitopes in general. Our new database now provides user-friendly comprehensive information about human CD CRDs and glycan epitopes (glycotopes) and additionally links to other resources. Carbohydrate recognition CD The carbohydrate recognition CD section contains: (1) lectin CDs that are classified within distinct lectin families such as selectins or siglecs. (2) CD antigens other than lectin families that have a carbohydrate recognition domain (CRD) defined by sequence homologies. For some of these, a functional influence of the CRD has not yet been clarified. (3) CD proteins that are related to carbohydrate binding, in the way that interactions with glycan moieties of other antigens influence their functional activities. There are 44-carbohydrate recognition CDs reported in this section. Users can search these data from the Browse menu. Each set of data in this section contains information about synonyms of this particular CD protein, its structure (also, three dimensional information wherever available), amino acid and nucleic acid sequence, cellular and tissue expression, function (and clinical application), references, carbohydrate and other possible ligands and further links to glycan array data. In glycan array information, it has been linked to the Consortium of Functional Glycomics database (Raman et al., 2006) and the Glyaffinity database (Frank and Schloissnig, 2010). There is also a small feature for finding interactions of non-GlycoCD/molecules with GlycoCD. Glycan CD Here, glycan CDs that define oligosaccharide moieties linked to glycoproteins and/or glycosphingolipids are included. There are 19 CDs reported in this section. Most of the CDs of this section interact with several molecules. We have given information about ligands if available or else linked it to the glycan array database Glyaffinity for relative affinity data. Users can search these data from the Browse menu. Each set of data in this section contains information about Glycotope (the carbohydrate epitope recognized by the respective CD-antibody), synonyms of the particular CD, its molecular structure, cellular and tissue expression, function (and clinical application), ligands and useful references, further links to GlycomeDB structure database (Ranzinger et al., 2008) with their ids, Glycosciences.de structural database and to glycan array data. We dedicate this database to Walter Knapp (deceased 2004) who initiated the organization of the HLDA conferences and workshops and to David Y.Mason (deceased 2008) who contributed significantly to the establishment of CDs and the organization of the conferences. We remember both not only as excellent leaders in this field but also as warm hearted persons with a great sense of humour. Funding: The European Commissions Seventh Framework Programme FP7/2007-2013, (215536). Conflict of Interest: none declared.


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Sonu Kumar, Thomas Lütteke, Reinhard Schwartz-Albiez. GlycoCD: a repository for carbohydrate-related CD antigens, Bioinformatics, 2012, 2553-2555, DOI: 10.1093/bioinformatics/bts481