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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 5 th of Dec 2016 1

Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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Page 1: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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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Page 2: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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)

Page 3: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

Data availability (from ELIXIR form)

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Page 4: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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

Page 5: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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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Page 6: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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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Page 7: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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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Page 9: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

Targets

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Page 10: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

Complementary target coverage:selectable UniProt cross-references

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Page 11: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

Ligands

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Page 12: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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

Page 13: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

GtoPdb curated small-molecules in PubChem: Useful intersects and diffs

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Page 14: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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

Page 15: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

Usage stats

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Page 16: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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)

Page 17: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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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Page 18: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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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Page 19: Introducing the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)

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