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GtoPdb Database Status Report - April 2019

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Database status report for GtoPdb from our April 2019 meeting in Paris

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GtoPdb Database Status Report - April 2019

  1. 1. Database progress reports
  2. 2. Overview 1. Database team activities 2. Web interface 3. Content expansion and updates 4. Concise Guide to PHARMACOLOGY (CGtP) 2019/20 5. Additional developmental and curatorial updates: ◦ IUPHAR Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb) ◦ IUPHAR/MMV Guide to MALARIA PHARMACOLOGY (GtoMPdb)  Please consult the accompanying April 2019 database report for more in-depth detail  We encourage discussion throughout this presentation – please interrupt us
  3. 3. Database team activities
  4. 4. Publications ◦ A new guide to immunopharmacology. Simon D. Harding, Elena Faccenda, Chris Southan, Pasquale Maffia, Jamie A. Davies. Nature Reviews Immunology (Web Watch). PMID: 30327546. ◦ SynPharm: A Guide to PHARMACOLOGY Database Tool for Designing Drug Control into Engineered Proteins. Sam Ireland, Christopher Southan, Alazne Dominguez, Simon Harding, Joanna Sharman, Jamie Davies. ACS Omega. Jul 31;3(7):7993-8002. PMID: 30087931 ◦ Challenges of connecting chemistry to pharmacology: perspectives from curating the IUPHAR/BPS Guide to PHARMACOLOGY. Christopher Southan, Joanna L Sharman, Elena Faccenda, Adam J Pawson, Simon D Harding, Jamie A Davies. ACS Omega. Jul 31;3(7):8408-8420. PMID:30087946 ◦ Accessing expert-curated pharmacological data in the IUPHAR/BPS Guide to PHARMACOLOGY. Joanna L Sharman, Elena Faccenda, Simon D Harding, Adam J Pawson, Christopher Southan, Jamie A Davies and NC-IUPHAR (2018). Current Protocols in Bioinformatics. 61: 1.34.1-1.34.46. PMID:30040201 ◦ Caveat usor: assessing differences between major chemistry databases. Chris Southan. ChemMedChem, 13(6):470-481. PMID 29451740
  5. 5. Public engagement ◦ Edinburgh Infectious Diseases 8th Annual Symposium, June 2019. Jane Armstrong will present a poster on the Guide to MALARIA PHARMACOLOGY ◦ BioMalPar XV: Biology and Pathology of the Malaria Parasite, EMBL, Heidelberg, May 2019. Jane Armstrong will present a poster on the Guide to MALARIA PHARMACOLOGY ◦ BPS Pharmacology 2018, London, UK, Dec 2018. Simon Harding, Chris Southan, Jamie Davies ◦ 5th European Congress of Immunology, Amsterdam, September 2018, Simon Harding - presented poster on the Guide to IMMUNOPHARMACOLOGY ◦ 18th World Congress of Basic and Clinical Pharmacology, July 2018, Kyoto, Adam Pawson and Chris Southan were in a Symposium on Computational Pharmacology, Databases and Drug Discovery, and had two talks and several posters ◦ ELIXIR All Hands 2018, Berlin, June 2018, Simon Harding ◦ Pharmacology Futures, Edinburgh, May 2018, Adam Pawson, Chris Southan, Jamie Davies
  6. 6. Outreach and social media FACEBOOK: The number of ‘likes’ increased to 4107 (March 2019), from 3749 in Sep 2018 TWITTER: @GuidetoPHARM has just pipped 1,900 tweets, followers have increased to 2670 from 2186 in Sep 2018 and our re-tweet rate has also gone up LINKEDIN: The Curation Team have been encouraging Subcommittee Chairs and collaborators to increase their reciprocal connectivity as individual LinkedIN users. This expands our collective inter-network outreach for posting updates, new papers, etc. BLOGGING: The Curation Team blog (http://blog.guidetopharmacology.org/) was receiving over ~670 views per month over the last 6 months. This is our primary news feed, includes database release updates, new features, technical items or articles HOT TOPICS: As an established and popular feature, our Hot Topics are seeded in the form of new significant pharmacology, drug discovery and key human genomics papers. These are communicated to us from NC-IUPHAR and Subcommittee members, or picked up from Twitter SLIDESHARE: Our account (http://www.slideshare.net/GuidetoPHAR M) allows the database team to share slide sets and posters with the community thereby extending the reach way beyond conference session direct attendees. Our slide sets received 3,444 (+486) views over the past year
  7. 7. Interactions with database users ◦ We get a steady stream of user communications coming in to enquiries@guidetopharmacology.org ◦ This is about one a week and they continue to cover a useful spectrum of (mostly minor) fixes that we promptly address ◦ It is useful to catalogue these engagements as they provide valuable information (not readily captured by analytics) in how and why GtoPdb is used ◦ They also provide useful ideas for future development ◦ Some examples of the above are in the accompanying report ◦ Additionally, we also receive a steady stream of emails from BJP/BJCP authors enquiring alerting us to missing links for ‘key’ ligands and targets for possible inclusion in accepted articles ◦ In appropriate cases, we then add these entities and the new reference
  8. 8. Interactions with other resources ELIXIR: Engagements continue with this important Europe- wide bioinformatics infrastructure initiative. GtoPdb is a UK Node Resource. https://elixiruknode.org/ PUBCHEM: We continue our important interactions with PubChem, including by both mail and TC conversations with Evan Bolton, Paul Theissen and other members of the team IUPHAR PHARMACOLOGY EDUCATION PROJECT (PEP): The IUPHAR Pharmacology Education project continues to be developed “as a learning resource to support education and training in pharmacological sciences”. The PEP celebrated its 4th birthday on 1st April 2019 JOURNAL < - > DATABASE CONNECTIVITY: The journal-to-GtoPdb linking initiative PMID 25965085) for the BJP since Oct 2014 and BJCP since Nov 2016, can be counted via the reference citations to our Concise Guide and NAR papers. The results indicate outlinks for ~ 80% of BJP papers and ~ 50% for BJCP
  9. 9. Skye/Links Project • Skye: ERC Consolidator Grant (James Cheney) to develop programming language support for data curation. Dr. Simon Fowler is the post-doc working on this. • Links: Research programming language with support for multi- tier web programming, language integration, and provenance tracking • Aims: • Reimplement GtoPdb in Links • Apply language features to a real-world scientific database • Identify new language features useful for data curators • Progress: Most core functionality implemented; hoping to start on curation interface soon
  10. 10. Skye/Links Project • http://homepages.inf.ed.ac.uk/jcheney/group/skye.html • Re-implementation of GtoPdb is useful to stress-test Links. It is the largest real-world application ever written in Links • Real benefit could be implementation of archiving and provenance tracking within the curation tool • Feedback from Simon Fowler describes the database schema of GtoPdb as ‘excellent’ and ‘very easy to understand and work with’.
  11. 11. Interactions with suppliers ◦ In May 2018 we accepted sponsorship from Tocris (https://www.tocris.com) in return for providing product supplier links on our ligand summary pages ◦ This sponsorship was limited to one year. In total, we mapped 1258 GtoPdb ligand to Tocris compounds ◦ We have agreed to continue this arrangement and update these sponsored links. We have begun preparations for the update and have been provided with an updated set of compounds from Tocris. These currently map to 1369 GtoPdb ligands. The new links will go live in May 2019
  12. 12. Web interface
  13. 13. Database access statistics Monthly statistics Apr 2018 - Mar 2019 (previous 12 months) Sessions 33,671 (31,255) Users 22,071 (20,293) Page views 115,765 (16,939) Pages / Session 3.44 (3.42) Avg. Session Duration 00:03:22 (00:03:18)
  14. 14. Acquisition, browsers and devices ◦ It is useful to be aware of where users are accessing GtoPdb and what devices/browsers they are using ◦ This can help us to better optimise the site and to ensure we test across the most popular platforms ◦ The majority of sessions on GtoPdb come via organic search (Google) and are performed predominantly from desktop devices. Chrome is also the browse of choice
  15. 15. Acquisition data, Apr 2018 - Mar 2019
  16. 16. Browser and Device Category of session, Apr 2018 - Mar 2019
  17. 17. File download statistics Count 2017-2018 2,810 2018-2019 2,704 Change -3.77% 2017-2018 2018-2019 Change Targets CSV/TSV file 1084 1085 no change Interactions CSV/TSV file 345 352 2% Ligands CSV/TSV file 250 254 1.6% UniProt Mapping file 165 170 3% HGNC mapping file 98 118 20% Peptides CSV file 99 121 22% PostgreSQL* 160 227 41% Generic slides (PPT & PDF) 234 196 -16% Generic poster 104 75 -27% Other files Tutorial 492 472 -4% Terms and Symbols 285 285 no change
  18. 18. Web services statistics ◦ Tracking of our web-services has been in place since March 2017 ◦ Calls to the web-service are generally from client computers to our server and are not recorded in the same way as visits to our website ◦ Therefore, we can’t report details on specific users, such as location or number of visits; only record the number of hits for each distinct URL ◦ There were approximately 105,000 total hits over the year, an increase of around 13% on the previous period ◦ Calls to target and ligands saw a reduction, but we note an increase in calls to interaction data and ligand similarity ◦ There was also a large increase in web service calls for ligand substructures, diseases and database links
  19. 19. New features and developments Web services: As part of the development of the GtoImmuPdb we have added target and ligands of immunological relevance, as well as the new immunopharmacology data types to our web services Renewal of supplier links: Already mentioned Converting to HTTPS: Using HTTPS (secure connection) on websites is becoming increasingly important (browsers and search engines are starting to warn users when they access an insecure site). Working with UoE Information Services, this is now at the final stage of implementation ChEMBL target links: We have updated all our outgoing target links to ChEMBL based on the most recent ChEMBL release (ChEMBL 25) Switch to using Chemicalize Pro (ChemAxon): A key feature of the IUPHAR Guide to Pharmacology website is the ability to perform searches by chemical structure (http://www.guidetopharmacology.org/GRAC/chemSearch.js p). The chemical structure search tool utilises Marvin JS by ChemAxon. In the 2019.1 release we have updated the API control to use Chemicalize Pro (https://pro.chemicalize.com/). This update simplifies the integration of Marvin JS into our website Update CDK libraries: We have updated the Chemical Development Kit (CDK) library to version 2.2. This is used by the Guide to Pharmacology to calculate molecular properties of ligands curated in the database. As part of this update, we performed a re-calculation of all molecular properties in the database Endogenous ligands: A new download file has been made available on our downloads page. This file contains a list of all ligands marked in the database as endogenous or natural ligands for a given target Transduction mechanisms: We have undertaken curatorial work to consolidate our curated data on GPCR transduction mechanism. In some cases, the database contained inconsistent data between the transduction mechanism data on a targets detailed view and its concise view. Our analysis identified these cases and we’ve put in place curatorial protocols to fix Page Navigation: We have updated our web-pages to feature a drop-down navigation bar, which is revealed when users scroll-down on longer pages. Many pages on GtoPdb are quite long, particularly detailed targets pages (e.g. CB1 receptor) – the new drop-down menu keeps key menu items, and most importantly the site search, in focus at all time
  20. 20. GtoPdb Navigation Drop-down navigation bar keeps search and help accessible Return to top quick-link useful on long detailed view pages
  21. 21. RDF We continue to keep the RDF version of the Guide to Pharmacology up-to-date at each release. We have implemented an ‘early-stage’ SPARQL endpoint that uses LodeStar as the web-application layer on top of the triple store. This provides a graphical frontend to the RDF data and allows control over SPARQL queries and provides the data in a human- readable format. This can be accessed at http://rdf.guidetopharmacology.org/
  22. 22. RDF
  23. 23. RDF
  24. 24. Content expansion and updates
  25. 25. Entity growth ◦ New entities are being added via Subcommittee updates and the population of GtoImmuPdb/GtoMPdb, and curator literature trawling ◦ Significant curation effort goes towards tagging pre-existing targets and ligands with comments and references to GtoImmuPdb and GtoMPdb Oct 2013 Oct 2015 April 2016 Oct 2016 Apr 2017 Oct 2017 May 2018 Sep 2018 Mar 2019 Target protein IDs 2485 2761 2775 2794 2808 2825 2872 2880 2920 Ligands total 6064 8024 8400 8674 8872 8978 9251 9405 9662 Approved drugs 559 1233 1273 1291 1322 1334 1364 1386 1421 Antibodies 10 138 172 205 212 223 240 248 255 Peptides 1776 1981 2007 2039 2063 2079 2092 2100 2122 Synthetic small molecules 3504 5055 5363 5563 5729 5807 6048 6180 6401 PubChem SIDs 3107 8024 8328 8674 8831 8978 9251 9405 9662 PubChem CIDs 2694 6057 6163 6337 6813 6822 7109 7224 7407 Binding constants 41076 44691 45534 45908 46287 46488 47058 47426 48071 References 21774 27880 29247 30251 31239 31733 33245 34382 35723
  26. 26. Target updates GPCRs: Acetylcholine receptors (muscarinic) Adenosine receptors Bradykinin receptors Cannabinoid receptors Chemokine receptors Class Frizzled GPCRs Leukotriene receptors Lysophospholipid (LPA, S1P) receptors Metabotropic glutamate receptors Neuromedin U receptors Neuropeptide S receptor Parathyroid hormone receptors Prostanoid receptors Proteinase-activated receptors Somatostatin receptors Tachykinin receptors Channels: Aquaporins Piezo channels Transient Receptor Potential channels Voltage-gated calcium channels Voltage-gated sodium channels NHRs: Androgen receptor Farnesoid X receptor Retinoic acid-related orphans Retinoid X receptors Enzymes: Endocannabinoid turnover Histone deacetylases (HDACs) Histone demethylases Fatty acid amide hydrolase (FAAH) Sugar phosphatases Dioxygenases Oxidoreductases Janus kinase (JakA) family Carbonic anhydrases Cytochrome P450s Adenylyl cyclases (ACs) Sphingosine kinases Cyclooxygenases 2-Acylglycerol ester turnover Eicosanoid turnover Other protein targets: Immune checkpoint proteins CD molecules Heat shock proteins Non-catalytic pattern recognition receptors STAT transcription factors
  27. 27. New targets (not including Antimalarial targets): ◦ Poly ADP-ribose polymerases ◦ Prolyl hydroxylases ◦ Carbonic anhydrases ◦ Paraoxonases ◦ Vanin 1 ◦ AQP11 ◦ NRF2 ◦ CA IX ◦ KIR3DL2 (CD158K) ◦ AC10 (adenylyl cyclase 10) ◦ αβ-Hydrolase 12 ◦ PVRIG ◦ C-type lectin domain family 12 member A
  28. 28. Relative target growth and coverage ◦ This can be assessed by comparing our own UniProt Human Swiss-Prot cross- references for targets with quantitative interactions against the other major chemogenomic resources that also have such cross-references; DrugBank, BindingDB and ChEMBL
  29. 29. ◦ The stats for the 2019.2 release (with 2018.4 in brackets) are as follows (N.B. because the NCBI Entrez system suffers from overload the links below may time out but should eventually return the result). ◦ Substances (SID) that we submit to PubChem (refreshing previous submissions) are up to 9670 (9251). ◦ Those that have defined chemical structures are merged into 7478 (6969) Compound Identifiers, CIDs (i.e. small molecules and moderate peptides) ◦ The select "IUPHAR/BPS Guide to PHARMACOLOGY"[SourceName] AND approved [Comment] now retrieves 1518 SIDs (1457) . ◦ Of these 1328 (1278) have CIDs (use the “Find Related Data” operator and select “same CIDs”. ◦ Of our SIDs, 1151 (993) are tagged in GtoImmuPdb and 282 (258) of these are approved drugs ◦ Of our CIDs 724 are tagged in GtoImmuPdb ◦ Of our SIDs, 57 are tagged in GtoMPdb and 19 of these are approved drugs ◦ Of our CIDs 51 are tagged in GtoMPdb ◦ We have 1817 (1675) structures that ChEMBL23 does not have, 5456 not in DrugBank and 6151 not in DrugCentral. ◦ 182 (95) structures unique to us as a source. ◦ PubChem has released a new interface that expands the indexing and search functionality for our own entries (see example query beside) but there are still some minor discrepancies in the exact metrics returned compared to the Entrez interface. PubChem statistics
  30. 30. Status of core subcommittees NC-IUPHAR Subcommittee Chairs/Liaisons (>90 subcommittees; ~500 scientists) G protein-coupled receptors Subcommittees Arthur Christopoulos and Anthony Davenport (Liaisons for all GPCR subcommittees) 5-Hydroxytryptamine:Nick Barnes; Daniel Hoyer Acetylcholine (muscarinic):Arthur Christopoulos Adenosine: Adriaan Izjerman alpha1-adrenoceptors: Roger Summers alpha2-adrenoceptors: Mika Scheinin Angiotensin: Sadashiva Karnik Apelin: Anthony Davenport beta-adrenoceptors: Martin Michel Bile acid: Anthony Davenport Bombesin: Robert Jensen Bradykinin: Réjean Couture Calcitonin: Debbie Hay, David Poyner Calcium-sensing: Hans Bräuner-Osborne; Katie Leach Cannabinoid: Roger Pertwee, Allyn Howlett Chemokine: Philip Murphy Cholecystokinin: Laurence Miller Complement peptide: Peter Monk; Trent Woodruff Corticotropin-releasing factor: Richard Hauger, Frank Dautzenberg Dopamine: Raul Gainetdinov Endothelin: Anthony Davenport G protein-coupled estrogen receptor: Eric Prossnitz Formylpeptide family: Richard Ye Free fatty acid: Leigh Stoddart;Nicholas Holliday Frizzled: Gunnar Schulte GABAB: Bernhard Bettler Galanin: Andrew Gundlach Ghrelin: Birgitte Holst Glucagon receptor family: Laurence Miller Glycoprotein hormone: Deborah Segaloff Gonadotrophin-releasing hormone: Adriaan Ijzerman Histamine:Paul Chazot; Rob Leurs Hydroxycarboxylic acid: Stefan Offermanns Kisspeptin: Anthony Davenport Leukotriene: Magnus Bäck Lysophospholipid (LPA): Jerold Chung Lysophospholipid (S1P): Sarah Spiegel Melanin-concentrating hormone: Jean-Louis Nahon Melanocortin: Tung Fong, Helgi Schiöth Melatonin: Ralf Jockers Metabotropic glutamate: Cyril Goudet Motilin: Anthony Davenport Neuromedin U: Gary Willars Neuropeptide FF/neuropeptide AF: Jean-Marie Zajac Neuropeptide S: Girolamo Calơ Neuropeptide W/neuropeptide B: Anthony Davenport Neuropeptide Y: Dan Larhammar Neurotensin: Jean Mazella Opioid:Larry Toll Orexin: Christopher Winrow P2Y: Maria-Pia Abbracchio; Kenneth A. Jacobson Parathyroid hormone: Jean-Pierre Vilardaga QRFP receptor: Jerome Leprince Platelet-activating factor: Satoshi Ishii Prokineticin: Philippe Rondard Prolactin-releasing peptide: Helgi Schiöth Prostanoid: Xavier Norel Protease-activated:Nigel Bunnett Relaxin family peptide: Roger Summers Relaxin-like: Nick Barker Somatostatin: Stephan Schulz Tachykinin: Susan Leeman, Steven Douglas Trace amine: Janet Maguire Thyrotropin-releasing hormone: Marvin Gershengorn Urotensin: Hubert Vaudry Vasopressin and oxytocin: Stephen Lolait VIP and PACAP: Joseph Pisegna Ligand-gatedion channels Subcommittees John Peters (Liaison for all LGIC subcommittees) Voltage-gatedion channels Subcommittees Joerg Striessnig (Liaison for all VGIC subcommittees) Nuclear hormone receptors Subcommittees John Cidlowski and Thomas Burris (Liaisons for all NHR subcommittees) 5-HT3: John Peters Acid-sensing (proton-gated) ion channels (ASICs): Stephan Kellenberger Epithelial sodium channel (ENaC): Israel Hanukoglu GABAA: Richard Olsen Glycine: Joseph Lynch Ionotropic glutamate: Graham Collingridge Nicotinic acetylcholine: Neil Millar P2X: Charles Kennedy; Michael Jarvis ZAC: Paul Davies Antibodies Subcommittee Alex Phipps; Michael Spedding Adenylyl cyclases Subcommittee Carmen Dessauer Drug Target and Chemistry Curation Subcommittee Christopher Southan Calcium-and sodium-activated potassium: Leonard Kaczmarek CatSper and Two-Pore: Dejian Ren Cyclic nucleotide-regulated: Martin Biel Inwardly rectifying potassium: Paul Slesinger Transient Receptor Potential: Haoxing Xu Two-P potassium: Steven Goldstein Voltage-gated calcium: William Catterall Voltage-gated potassium: Lily Jan Voltage-gated sodium: William Catterall ‘Gasotransmitters’ Subcommittee Andreas Papapetropoulos and Csaba Szabo Guanylyl cyclases Subcommittee Adrian Hobbs and Scott Waldman Non-coding RNAs Subcommittee Andrew Baker NHR subcommittees under review Epigenetics and Kinase Subcommittee Doriano Fabbro Pattern Recognition Receptors Subcommittee Clare Bryant Proteases and Hydrolases Subcommittee Christopher Southan Transporters Subcommittees Stephen Alexander (Liaison for all Transporter subcommittees Data Interoperability Subcommittee Alasdair Gray Concise Guide to PHARMACOLOGYEditors Stephen Alexander, Eamonn Kelly, John Peters
  31. 31. GPCRs Liaisons: Arthur Christopoulos and Anthony Davenport Updates since October 2018 Acetylcholine receptors (muscarinic), Adenosine receptors, Bradykinin receptors, Cannabinoid receptors, Chemokine receptors, Class Frizzled GPCRs, Leukotriene receptors, Lysophospholipid (LPA, S1P) receptors, Metabotropic glutamate receptors, Neuromedin U receptors, Neuropeptide S receptor, Parathyroid hormone receptors, Prostanoid receptors, Proteinase-activated receptors, Somatostatin receptors, Tachykinin receptors Ongoing major revision Acetylcholine receptors (muscarinic), Bradykinin receptors, Somatostatin receptors New Subcommittee, Chairpersons, Members Réjean Couture (Bradykinin) is joined by Fernand Gobeil, Peter Monk (Complement peptide) is replaced by Trent Woodruff Problem areas Birgitte Holst (Ghrelin), Jean Marie Zajac (NPFF/AF), Dan Larhammar (NPY), Satoshi Ishii (PAF), Joseph Pisegna (VIP/PACAP)
  32. 32. VGICs Liaison: Jörg Striessnig Family Subcommittee Chair Required CatSper and Two-Pore channels Dejian Ren Review/update Cyclic nucleotide-regulated channels Martin Biel Review/update Calcium- and sodium-activated potassium channels Leonard Kaczmarek Review/update Inwardly rectifying potassium channels Paul Slesinger Review/update Two P domain potassium channels Steve Goldstein Review/update Voltage-gated potassium channels Lily Jan Review/update Ryanodine receptors Isaac Pessah (UC Davis) NEW! Transient Receptor Potential channels Haoxing Xu Review/update Voltage-gated calcium channels Jörg Striessnig Review/update Voltage-gated proton channel Thomas DeCoursey (Rush U) ? Voltage-gated sodium channels Bill Catterall Review/update
  33. 33. LGICs Liaison: John Peters Family Subcommittee Chair Required 5-HT3 receptors John Peters, Tim Hales Review/update Acid-sensing (proton-gated) ion channels (ASICs) Stephan Kellenberger, Lachlan Rash Review/update Epithelial sodium channel (ENaC) Israel Hanukoglu Review/update GABAA receptors Werner Sieghart Review/update Glycine receptors Joseph Lynch, Lucia Sivilotti, Trevor Smart Review/update Ionotropic glutamate receptors Review/update IP3 receptor Review/update Nicotinic acetylcholine receptors Neil Millar Review/update P2X receptors Charles Kennedy, Michael Jarvis Review/update ZAC Paul Davies, Anders Jensen Review/update
  34. 34. NHRs Liaisons: John Cidlowski and Tom Burris Family Contact Liaison Required 1A. Thyroid hormone receptors Douglas Forrest John Cidlowski Review/update 1B. Retinoic acid receptors Tom Burris Review/update 1C. Peroxisome proliferator-activated receptors Tom Burris Review/update 1D. Rev-Erb receptors Tom Burris Review/update 1F. Retinoic acid-related orphans Anton Jetten John Cidlowski Review/update 1H. Liver X receptor-like receptors Donald McDonnell John Cidlowski Review/update 1I. Vitamin D receptor-like receptors J. Wesley Pike, Sylvia Christakos John Cidlowski Review/update 2A. Hepatocyte nuclear factor-4 receptors Frances Sladek John Cidlowski Review/update 2B. Retinoid X receptors Tom Burris Review/update 2C. Testicular receptors Tom Burris Review/update 2E. Tailless-like receptors Tom Burris Review/update 2F. COUP-TF-like receptors Sophia Tsai, Ming-Jer Tsai John Cidlowski Review/update 3B. Estrogen-related receptors Tom Burris Review/update 4A. Nerve growth factor IB-like receptors Tom Burris Review/update 5A. Fushi tarazu F1-like receptors Tom Burris Review/update 6A. Germ cell nuclear factor receptors Tom Burris Review/update 0B. DAX-like receptors Tom Burris Review/update Steroid hormone receptors John Cidlowski Review/update 3A. Estrogen receptors Kenneth Korach, Laurel Koons John Cidlowski Review/update 3C. 3-Ketosteroid receptors (Androgen receptor ) Nancy Weigel John Cidlowski Review/update 3C. 3-Ketosteroid receptors (Glucocorticoid receptor) Robert Oakley, Derek Cain John Cidlowski Review/update 3C. 3-Ketosteroid receptors (Mineralocorticoid receptor) Peter Fuller, Morag Young John Cidlowski Review/update 3C. 3-Ketosteroid receptors (Progesterone receptor) Dean Edwards John Cidlowski Review/update
  35. 35. Additional new subcommittee chairs Endocannabinoid turnover – Patrick Doherty and Christopher Fowler are replaced by Mario van der Stelt (Leiden) and Jürg Gertsch (Bern)
  36. 36. CGtP 2019/20
  37. 37. CGtP 2017/18
  38. 38. CGtP 2019/20 planning Editorial Stage 15 September 2018 Deadline for editors to agree any formatting changes 30 September 2018 Team start to agree new targets (mostly based on the emails AP gets informing that targets in their articles aren’t in the database) – allow some flexibility later on so that we don’t miss really important new targets = NEW TARGET LOCKDOWN 15-26 October 2018 Editors to be sent PDF templates (via PDF OUTBOX, in shared folders) to review and add comments before they are sent to collaborators for updates 1 November 2018 Kick-off at GtoPdb – 1st call for updates 3 January 2019 2nd call for updates 31 January 2019 Deadline for receipt of updates Publication Stage 8 March 2019 Deadline for updates to be completed in the database (i.e. all the sections that will be uploaded for the CGtP by the early-May deadline) = DATABASE LOCKDOWN 8 May 2019 Final full LaTeX version of all chapters to be supplied to Wiley, alongside introduction section and abstracts for each section 8 May 2019 Full list of Editors and Collaborators (including affiliations and ORCID IDs) and curators to be sent to Wiley 9 June 2019 Complete set of proofs (including covers and front matter) to be sent to the Editors for review (subsequent rounds of proofing will be required) 10 July 2019 Final deadline for corrections. No further revisions to proofs after this date 9 September 2019 (approximate) Online publication CGtP 2019/20
  39. 39. CGtP 2019/20 - Editorial stage ◦ Editorial deadlines were brought forward by 2 weeks ◦ General guidelines from editors to collaborators were updated ◦ Email campaign: ◦ A PDF file of the target family summary page that has been generated from the online summary view ◦ General Guidelines for providing the update, including instructions on how to annotate the attached PDF file using Adobe Acrobat Reader ◦ An Excel file for listing the Collaborators who contribute to this update, and for providing consent to be listed as a Collaborator ◦ 233 updates requested; 172 ‘tangible’ updates received
  40. 40. CGtP 2019/20 - Publication stage ◦ Chapter organisation: Reducing from 9 to 7 chapters; one Ion Channels chapter (‘Voltage-gated’, ‘Ligand-gated’ and ‘Other’) ◦ Recognition of the collaborators: in the form of citations for their contributions ◦ Collaborators must provide consent at time of submitting updates ◦ Collaborators to be listed against relevant chapter (instead of the ‘Overview’) ◦ Ensuring authorship is transmitted to PubMed, Web of Science and Google Scholar – all of which can be used by authors to determine their H index ◦ The 2019/20 edition of the ‘Concise Guide’ is set for publication in September 2019 ◦ Marketing plan: ◦ Wiley using similar marketing strategy to the successful one employed for the CGtP 2017/18 ◦ Mailing lists for printed copies and USBs, also available at conferences and for teaching ◦ Review the list of Pharma companies targeted for marketing; use Clarivate to identify individual researchers within these companies to target for marketing; noted that print materials are attractive to industry professionals for data protection reasons ◦ Identify Societies that should be sent print copies
  41. 41. IUPHAR Guide to Immunopharmacology (GtoImmuPdb) DEVELOPMENTS AND UPDATE
  42. 42. GtoImmuPdb Launch Official launch in October 2018 in Edinburgh Full Report and presentations at https://www.guidetoimmunopharmacology.org/immuno/immuphar2018.jsp Prof. Tracy Hussell delivered the Anthony Harmer Memorial Lecture: Decision-making in lung immunity
  43. 43. GtoImmuPdb Portal Inclusion of CVR OnLife Interview Links with Immunopaedia
  44. 44. Immunopaedia Link between Immunopaedia Case-Studies and GtoImmuPdb Ligand and Targets. • Immunopaedia mark-up case studies • GtoPdb curate these and feedback • Links added to GtoPdb database • Displayed under Immunopharmacology tab on ligand summary page Promotes education, knowledge and research in Immunology globally. Official provider for online courses for IUIS
  45. 45. Immunopaedia
  46. 46. GtoImmuPdb Data Target Class Targets (593) Enzymes 193 Catalytic Receptors 148 GPCRs 100 Other Proteins 99 Ion Channels 39 Transporters 9 NHRs 8 Ligand Type Ligands (1150) Ligand assoc. To disease Synthetic Organic 710 236 Approved Drugs 254 191 Peptides 239 44 Antibodies 150 104 Metabolites 37 17 Natural Products 13 4 Inorganic 1 Annotations Targets Ligands Immunological Processes 3195 979 - Immunological Cell Types 323 151 - Diseases 56 / 714 38 407
  47. 47. GtoImmuPdb Data
  48. 48. GtoImmuPdb Data
  49. 49. GtoImmuPdb Data GtoImmuPdb has higher representation in Catalytic Receptor, Other Protein and (to a lesser extent) GPCR classes
  50. 50. GtoImmuPdb Data GtoImmuPdb has higher proportion of antibodies and slightly higher proportion of approved drugs.
  51. 51. GtoImmuPdb Access Approx. 1,100 sessions per month, with slightly higher engagement (page/session, duration) compared to GtoPdb. 6 months: October 2018 – March 2019
  52. 52. GtoImmuPdb Future Work Prepare manuscript on Guide to Immunopharmacology ◦ Aiming at Immunology journals/readers Continue collaborations with Immunopaedia Implement disease classification
  53. 53. IUPHAR/MMV Guide to Malaria Pharmacology (GtoMPdb) DEVELOPMENT
  54. 54. GtoMPdb Development Development builds on robust existing database schema and web- application code. Able to produce a new portal by following method used in generation of the Guide to Immunopharmacology.
  55. 55. GtoMPdb Portal www.guidetomalariapharmacology.org • Panels provide tailored routes for browsing antimalarial data: • Ligands • Targets • Parasite Lifecycle Stages • Target Species • The same categories can be accessed from the menu bar • Search (top right) is across GtoPdb and up-weights antimalarial data
  56. 56. GtoMPdb Ligand List • At present there are two categories: • The ‘Antimal’ tab provides a discrete list of all ligands that have the GtoMPdb tag • Approved tab • The ‘Antimal’ tab is also available on other Ligand List pages
  57. 57. GtoMPdb Detailed Target Page • Modelled on GtoPdb Detailed Target page • Shows all curated information that our database holds about the target • Includes links to PlasmoDB, UniProt and where available PDB PfPNP (ID: 3077) www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForw ard?objectId=3077
  58. 58. GtoMPdb Detailed Target Page New comments section for information of particular relevance to malaria Interactions table includes Whole Organism Assay data
  59. 59. Parasite Lifecycle Stage malaria_stage name description malaria_stage2interaction interaction • Two new database tables to describe parasite lifecycle stages and link to interaction data • New functions in curators submission tool to indicate malaria lifecycle stage
  60. 60. Parasite Lifecycle Stage malaria_stage name description malaria_stage2interaction interaction • Two new database tables to describe parasite lifecycle stages and link to interaction data • New functions in curators submission tool to indicate malaria lifecycle stage
  61. 61. Parasite Lifecycle Stage malaria_stage name description malaria_stage2interaction interaction Target/Ligand counts build on work from GtoImmuPdb Display of interactions uses code from detailed target pages/ligand summary pages
  62. 62. Target Species Pages Added description to species information, extending submission tool to capture Each Plasmodium strain is stored in the database as though a different species Interactions can then be annotated against specific species/strain The code can consolidate all data for a single species for display based on internal species ID
  63. 63. Target Species Pages Individual Species page Display of interactions uses code from detailed target pages/ligand summary pages New species description displayed at top of page. Species comment displayed in strain specific pop-up
  64. 64. GtoMPdb Search Site-search covers curator comments for targets and ligands Recently added parasite lifecycle stage names and descriptions plus target species names and abbreviations Search produced weighted results if executed from the GtoMPdb URL Results with relevance to Malaria Pharmacology up-weighted Next: • Add in advanced options, to filter search on targets/ligands • Incorporate assay descriptions • Continue testing
  65. 65. GtoMPdb Future Work (Dev) • Currently capturing detailed information within comments • Extend the database to have specific fields for these data • Good for search, web-services, analysis… • Examples: • Target Candidate Profile (TCP) • Parasite Reduction Ratio (PRR) • Parasite Clearance Time (PCT)
  66. 66. GtoMPdb Future Work (Dev) • Advanced Search • Review data captured in comments – is there anything we could store in discrete fields, e.g. Target Candidate Profiles (TCP). • Web Services – we need to add Malaria Pharmacology data to the API
  67. 67. IUPHAR/MMV Guide to Malaria Pharmacology (GtoMPdb) CURATORIAL ASPECTS
  68. 68. Collecting & Prioritising Content •Lists of antimalarial ligands and Plasmodium targets were collated during the pilot phase •We have continued to add to these lists and refine priorities •MMV have provided a list of high priority targets and advised on our pilot ligand list •EAC feedback •In addition, we use reference manager software to collect and precurate publications •Chris has collected over 200 publications that he has tagged with antimalarial specific tags
  69. 69. Content Expansion • Steady growth in the number of antimalarial ligands and Plasmodium targets • Our most recent database release (2019.2) contains: • 57 ligands tagged as in GtoMPdb • 25 targets tagged as in GtoMPdb • Our curated ligands include antimalarial leads, drugs in preclinical and clinical development and approved medicines
  70. 70. Content Expansion GtoPdb:Target Name GtoPdb:Target Name PfATP4 PfPI3K PfCARL PfPI4K PfCPSF3 PfPKG PfDHFR-TS PfPMX PfDHODH PfPN PfDXR PfPPPK-DHPS PfeEF2 PfSHMT PfGWT1 PfKRS1 PfHDAC1 PfcPheRS PfHDP PfPRS PfHT PfThrRS PfIspD PfV-type proton ATPase PfNMT
  71. 71. Next Steps • Curation: • Complete curation of targets from MMV’s priority list – we will exceed the number evaluated at the beginning of the project • Continue curation of ligands – we will meet the number evaluated at the beginning of the project • Outreach: • Press release to coincide with World Malaria Day 2019 • Poster presentation, BioMalPar XV: Biology and Pathology of the Malaria Parasite, May 2019 • Poster presentation, Edinburgh Infectious Diseases Annual Symposium, June 2019 • Portal development: • Improvements raised from user feedback • Extend the database to capture data that is currently in malaria comments section
  72. 72. Next Steps • Currently capturing detailed information within comments • Extend the database to have specific fields for these data • Good for search, web-services, analysis… • Examples: • Target Candidate Profile (TCP) • Parasite Reduction Ratio (PRR) • Parasite Clearance Time (PCT)
  73. 73. Acknowledgements All past and current members of NC-IUPHAR NC-IUPHAR subcommittees and Concise Guide to PHARMACOLOGY editors/contributors Database team: ◦ Jamie Davies (Principal Investigator) ◦ Joanna Sharman and Simon Harding (Developers) ◦ Adam Pawson, Jane Armstrong, Elena Faccenda, Christopher Southan (Curators) ◦ Tony Wigglesworth (Administrator) All past and current NC-IUPHAR and website sponsors Funders:

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