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Introducing the IUPHAR/BPS Guide to PHARMACOLOGY(GtoPdb)
http://www.guidetopharmacology.org/
Webinar presentation by Chris Southan
for ELIXIR-UK all-hands 5th of Dec 2016
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Who and where
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• Core team: Christopher Southan, Elena Faccenda, Simon J. Harding, Joanna L. Sharman, Adam J. Pawson, Prof. Jamie A Davies (PI and Grant holder)
• IUPHAR = International Union of Basic and Clinical Pharmacology
• NC-IUPHAR = Committee on Receptor Nomenclature and Drug Classification
• BPS = British Pharmacological Society
• BJP = British Journal of Pharmacology (Wiley, Oxford)
• Where: University of Edinburgh, Centre for Integrated Physiology, EH8 9XD, UK. (Chris works remotely from Göteborg, Sweden)
Data availability (from ELIXIR form)
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Database history
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• In 2012 GtoPdb became single entry point to previously separate but complementary information sources
• The IUPHAR database (IUPHAR-DB from 2009) • Guide to Receptors and Channels (GRAC) series of British Journal of
Pharmacology publications
NAR history
The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Southan et. al. Nucleic Acids Research [2016, 44(D1):D1054-68] (PMID:26464438) 8 citations (EPMC figures)
The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Pawson et al. Nucleic Acids Research [2014, 42(Database issue):D1098-106] (PMID:24234439) 359 citations
IUPHAR-DB: updated database content and new features. Sharman et al. Nucleic Acids Research [2013, 41(Database issue):D1083-8] (PMID:23087376) 33 citations
IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data. Sharman et al. Nucleic Acids Research [2011, 39(Database issue):D534-8] (PMID:21087994) 55 citations
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Remits
• Provide access to data on all known biological targets
• Populate the data records by expert curation
• Browsable by wide range of users (from students to Profs)
• Make recommendations on ligands for use in characterising targets
• Provide an entry point into the pharmacological literature
• From BJP papers and reviews to point “back” to database
• Provide an integrated educational resource for principles of basic and clinical pharmacology
• Distillation of selected content into the BJP “Consise Guide” bi-annual series of reviews
• Content fully open, downloadable and consumable
• Foster innovative drug discovery
• Tight liaison with NC-IPHAR and BPS
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Curating the core relationship chain
• Documents are mostly PubMed IDs but some patents also • Assay is implicitly described in each publication• Results typically recorded as IC50, Ki, Kd or EC50, log transformed to pAct (e.g.
4-10) • We define “ligand” as the implicit binding entity, mostly small-molecules but
some peptides, small proteins and therapeutic antibodies• Target usually resolved to a UniProt ID• Pick individual interactions from complexes where possible (e.g. PSEN1 for
gamma secretase)• Have some ligands with unknown molecular mechanism of action (mmoa)
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Targets
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Complementary target coverage:selectable UniProt cross-references
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Ligands
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GtoPdb drugs
• The PubChem query (approved[comment] AND "IUPHAR/BPS Guide to PHARMACOLOGY"[SourceName]) retrieves just our 1291 substances (SIDs)
• These convert to 1174 distinct compound entries (CIDs)
• 96% vendor matches in PubChem
• The 117 SID difference is mainly antibodies 12
Introduced a clean PubChem select for our drugs
GtoPdb curated small-molecules in PubChem: Useful intersects and diffs
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Recent curated relationship growth
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• Human proteins with quantitative interactions, including kinase screening data 1429
• Without kinase screening data it is 1322
Usage stats
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Unique to GtoPdb, NC-IUPHAR: part SAB, part “supercurator” network
• ~ 60 specialist subcommittees, mostly target family-centric• ~ 630 scientists globally• Send regular updates to be curated into the database
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(This is an older list now being updated)
The value of ecosystem in-links/cross-pointers
• We have a blog post describing these https://blog.guidetopharmacology.org/2016/03/30/collation-and-assessment-of-gtopdb-in-links/
• More that we suspected, probably others we are unaware of
• Includes PubChem, HGNC, UniProtKB/Swiss-Prot, neXtProt, IMGT/mAb-DB, ChEMBL, UniChem, MEROPS, GPCRdb, ChemSpider, Oprhanet, CARLSBAD, GLASS, ChemProt, ZINC, DGIdb 2.0 and DrugCentral
• We foster socio-collaborative contacts with most of these, via invitations to our bi-annual meetings, TCs and conference bar encounters
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Funding
• Wellcome Trust 099156/Z/12/Z Nov 2012 - 31 Oct 2015 to Prof Jamie Davis (taking over from the late Prof. Tony Harmar). University of Edinburgh IT infrastructure support .
• GtoPdb has also been supported by: The British Pharmacological Society (March 2011 - March 2015, and IUPHAR (March 2011 – March 2015).
• Current, November 2015 to October 2018, new Wellcome Trust 108420/Z/15/Z to extend GtoPdb into Immunopharmacology
• Servier Laboratories sponsorship of annual meeting
• The BPS supporting 2 FTEs (March 2016 – March 2020)
• Commitee, headed by Prof. Davies planning future options. Currently preparing Wellcome proposal “GtoAMPdb – a database of antimicrobials, targets, and mechanisms of resistance”
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Plans and issues
• Need to be RDF-ised
• As usual – limitations of curation capacity
• Manual vs auto (brainless) linking
• New data aspects obsoleting older content (e.g. expression data and clinical variants
• Analytics exposes legacy data issues that are difficult to remediate
• Impingement by other resources
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Thank you; questions welcome
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Didactic slide slide set from 2014http://www.slideshare.net/GuidetoPHARM/iupharbps-guide-to-pharmacology-generic-slideset
FAQhttp://www.guidetopharmacology.org/faq.jsp