GtoPdb_ITMAT_2017
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The document discusses the IUPHAR/BPS Guide to Pharmacology, which provides high-quality, unique data on ligand-receptor interactions and aims to support translational research in pharmacology. It emphasizes the importance of curated small data, reflecting its value as several databases reference it. The guide facilitates the identification of key compounds and integrates with big data resources for enhanced utility.
GtoPdb_ITMAT_2017
- 1. Christopher Southan1, Antony P. Davenport2, Joanna L. Sharman1, Adam J. Pawson1, Simon D. Harding1, Elena Faccenda1, Jamie A. Davies1 and NC-IUPHAR3. 1IUPHAR/BPS Guide to PHARMACOLOGY, Centre for Integrative Physiology, University of Edinburgh, EH8 9XD, UK. 2Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. 3The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification. The imperative of small, high quality data for underpinning big data: the IUPHAR/BPS Guide to PHARMACOLOGY Unique content • Part of our value derives from relationship mapping stringencies, expert comments and unique content • This uniqueness arises from journal selectivity and frequent quarterly releases capturing new publications • We have ligand binding interactions for over 70 human proteins that are neither in DrugBank nor ChEMBL • Figure 3 (below) provides a breakdown of our PubChem content that indicated aspects of uniqueness • We submit all our ligands (as SIDs) but some are too large to be assigned compound identifiers (CIDs) • Over 1000 of these are receptor-binding peptides from the pharmacological literature • 320 of our structures are unique in PubChem (total 94m) • Compared to DrugBank we differ by over ½ their content • We have 1,535 CIDs not in ChEMBL Examples of GPCR database tables Conclusions • The underpinning value of our “small data” quality is reflected in at least 15 other databases (e.g. UniChem, PubChem, ChEMBL, UniProt, HGNC, ChemProt and others) choosing to point their links to us • GtoPdb supports translational research with ligand binding data for rodent targets • We also recommend tool compounds for agonists, antagonists and radiolabelled ligands • Our data facilitates both direct mining and integration of quantitative pharmacology from the translational disciplines of chemical biology and genetics • We are increasing our “big data” utility by a) downloads and web services b) developing Resource Description Framework (RDF) for integration with other resources (e.g. OpenPhacts) and c) a Wellcome funded project to extend our existing schema into the immunopharmacology domain for expanded relationship capture Introduction • The Wellcome Trust funded International Union of Pharmacology (IUPHAR)/British Pharmacology Society (BPS) database (GtoPdb) www.guidetopharmacology.org • Provides annotated molecular interactions between endogenous receptor ligands, research compounds, approved drugs and their Swiss-Prot targets • Builds on the reputation of its predecessor IUPHAR-DB • Enables pharmacologists and other bioscientists to identify key compounds across target classes • Is being integrated into “big data” resources www.slideshare.net/GuidetoPHARM/gtopdbitmat2017 [email protected] Fig. 2. Breakdown of ligand by class in GtoPdb UK Node Resource for: Populating the database • As described in PMID 26464438, GtoPdb content is curated from pharmacology and medicinal chemistry journals, released quarterly, with PubChem updates • Quality is ensured by expert curation by a highly qualified team and our unique model of integrating recommendations and updates from IUPHAR target class subcommittees of international experts • We have connected ~14,000 binding values (mainly IC50, Ki, Kd) between ~8,000 ligands (see Fig. 1) and ~1,500 human proteins (see Fig. 2) thereby defining 7% of the druggable proteome • We curate out-links to a range of chemistry and protein databases where we have direct contacts Fig. 1. Breakdown of human targets in GtoPdb Fig. 3. GtoPdb ligands in PubChem