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GtoPdb_StatusReport_May2018_GtoImmuPdb

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Presented at our May NC-IUPHAR meeting in Edinburgh. Status Report on GtoImmuPdb

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GtoPdb_StatusReport_May2018_GtoImmuPdb

  1. 1. DATABASE STATUS REPORT GtoImmuPdb Simon Harding Elena Faccenda Christopher Southan 1
  2. 2. The Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb) 2
  3. 3. Overview • Database status reports (GtoImmuPdb) • Developmental aspects • Curatorial aspects • We encourage discussion throughout this presentation – please feel free to interrupt us! • Please consult the accompanying May 2018 database report for more in-depth detail 3
  4. 4. GtoImmuPdb DEVELOPMENT STATUS Simon Harding 4
  5. 5. Overview ● GtoImmuPdb Status ○ Analytics, User-Testing, Curation Stats ● Disease ○ Development and Data ○ Lists ○ Categorisation ○ Summary Pages ● Cell type data & graphical browsing ● Process data & GO evidence display ● Next steps 5
  6. 6. GtoImmuPdb Status www.guidetoimmunopharmacology.org ● First public release July 2017 (beta v1) ● Beta v2 (August 2017) ● Beta v3 (March 2018) ○ Currently user testing ○ Major development has been on Disease Data 6 • Beta v3 (Now) > Full Release (Imminent) > Official Launch (Oct 2018)
  7. 7. User-Testing GtoImmuPdb ● Undertook user-testing on GtoImmuPdb v3.0 ○ IUPHAR ImmuPhar Section ○ Contacts from BSI Congress 2017 ○ Reached out to British Society for Immunology regional groups ○ Limited response so far 7
  8. 8. GtoImmuPdb Analytics Google Analytics since July 2017 8 Average Per Month Users: 551 Sessions: 811 Most views from ● USA (22%) ● UK (14%) ● China (7%) ● India (5%) ● Germany ● France ● Japan The GtoImmuPdb Portal accounts for 12% of all traffic (3,625 views).
  9. 9. GtoImmuPdb Data: Stats 9 ● Current curation stats for GtoImmuPdb targets and ligands 525 targets in GtoImmuPdb Catalytic Receptors 145 Enzymes 168 GPCRs 94 Other Proteins 87 VGICs 17 NHRs 6 Transporters 5 LGICs 3 993 ligands in GtoImmuPdb Synthetic Organic 589 Peptides 228 Antibodies 138 Natural Products 11 Inorganic 1 www.guidetoimunopharmacology.org/immuno/immunoHelpPage.jsp#downloads
  10. 10. Disease Development 10 ● Major development in GtoImmuPdb beta v3 ● GtoPdb already contains over 1,000 disease terms associated to targets via pathophysiology and mutation data ● GtoImmuPdb development involves integration with the existing data structures, and building a single disease summary display DiseasePathophysiology Immuno Targets Immuno Ligands Mutation Targets Webpage Disease Summary Pages
  11. 11. Disease Data 11 Targets/Ligands Annotations Diseases Targets 35 53 27 Ligands 386 679 95 ● Summary of disease data in GtoImmuPdb
  12. 12. Disease Lists 12 http://www.guidetoimmunopharmacology.org/GRAC/DiseaseListForward?type=Immuno Disease list page ● Access from portal and menu-bar ● Alphabetical list ● Tabbed-categories (work-in-progress) ● Displays synonyms ● Displays counts of associated targets and ligands
  13. 13. Disease Categories 13 ● Categories will provide finding/browsing diseases easier ● Can have different categories for GtoImmuPdb / GtoPdb ● Use Disease Ontology to underpin categorisation
  14. 14. Disease Categories 14 Use top-level categories for GtoPdb Higher-resolution for GtoImmuPdb
  15. 15. Disease Categories 15 Hypersensitivity reaction disease ● Anaphylactic shock ● Alopecia areata ● Autoimmune lymphoproliferative syndrome ● Autoimmune thrombocytopenic purpura ● Celiac disease ● CINCA syndrome ● Graves’ disease ● Lupus erythematosus ● Myasthenia gravis ● Sarcoidosis ● Sjorgen’s syndrome ● Vitiligo ● Use first sub-level under ‘Immune System Disease’
  16. 16. Disease Categories 16 Intestinal Disease > Inflammatory Bowel Disease ● Colitis ● Crohn’s disease ● Inflammatory bowel disease 1; IBD1 ● Ulcerative colitis ● Not all ‘immune’ disease we have data for neatly fit under ‘Immune System Disease’ ● We can decide other nodes to include (i.e. IBD) Work-in-progress: Incorporate Disease Ontology relationships to support categorisation
  17. 17. Disease Summary Pages 17 Disease Summary page - Overview Contains 3 sections: Overview, Targets and Ligands http://www.guidetoimmunopharmacology.org/GRAC/DiseaseDisplayForward?diseaseId=801
  18. 18. Disease Summary Pages 18 Disease Summary page - Overview Contain 3 sections: Overview, Targets and Ligands Top section - summarises association data, give disease synonyms, description and links
  19. 19. Disease Summary Pages 19 Disease Summary page - Targets For each target any pathophysiology, mutation and immuno data (including interacting immuno ligands). Some associations with absent data Ligands with interaction data to target, and associated to disease highlighted Target-ligand associations not currently displayed
  20. 20. Disease Summary Pages 20 Disease Summary page - Target Ligands Example of fezakinumab and IL-22 Some associations with absent data Target-ligand associations not currently displayed
  21. 21. Disease Summary Pages 21 Disease Summary page - Ligands Nearly all ligand data as a consequence of GtoImmuPdb curation Summarises approval status, references and clinical comments Expandable comments sections Clinical use and GtoImmuPdb curated comments
  22. 22. Next steps – Disease ● Categorisation ● Implement disease name and synonym search ● Include target ligand associations in summary pages 22
  23. 23. Cell Type Data 23 Cell type category Targets annotated B cells 33 T cells 47 Dendritic cells 32 Other T cells 3 Macrophages & monocytes 43 Granulocytes 37 Natural killer cells 20 Mast cells 28 Innate lymphoid cells 2 Stromal cells 0 ● Curation stats for Cell Type Categories
  24. 24. Cell Type Data - Graphical Browse 24 http://www.guidetoimmunopharmacology.org/GRAC/CelltypesForward
  25. 25. Process Data 25 • Curation stats for Process Categories Process Top-Level Category GtoPdb Human UniProtKB Target-GO Annotation Barrier Integrity 46 59 Inflammation 605 1372 Antigen Presentation 169 242 T cell (activation) 185 384 B cell (activation) 149 245 Immune regulation 461 1190 Tissue repair 20 20 Immune system development 227 398 Cytokine production & signalling 452 1152 Chemotaxis & migration 243 423 Cellular signalling 465 1145
  26. 26. Process Data 26 ● Adjusted immuno process associations display ● IEA (Inferred by Electronic Annotation) hidden by default. ● “Assigned by automated methods, without curatorial judgement”
  27. 27. GtoImmuPdb Next Steps www.guidetoimmunopharmacology.org ● Continue testing to get feedback ● Disease searching ● Target-ligands on disease summary ● Extend pop-up help ● Help videos ● Prepare for October launch “Immunopharmacology Challenges” 27
  28. 28. GtoImmuPdb CURATORIAL STATUS Christopher Southan and Elena Faccenda 28
  29. 29. Overview • Searching • Expansion of the CiteUlike collection • Twitter • New ligand and target examples • Journal coverage • Ligands in PubChem • Achievements, issues and plans 29
  30. 30. Searching by conventional PubMed term query: high recall but low specificity for curatable papers 30 ~ 500 papers per month
  31. 31. tag > annotate > curate > share 31 • 921 “immpharm” tagged publications • Pre-curation tags, notes and post-curation pointers to entries
  32. 32. Twitter: good allerting efficiency 32
  33. 33. Further reading expansion 33 http://www.guidetoimmunopharmacology.org/GRAC/ImmunoFurtherReadingForward
  34. 34. Not selecting for curation also important 34
  35. 35. Target expansion 35 Gene symbol TID Protein name Curated ligands Mechanism of action/clinical relevance SIGIRR 2969 single Ig and TIR domain containing, IL-1R8 IL-37 is agonist Acts as a NK cell checkpoint, regulating anti-viral and anti-tumour effector functions of NK cells EPHX2 2970 epoxide hydrolase 2 2 inhibitors Participates in the regulation of prostaglandin and leukotriene production and therefore in immune homeostasis CHIA 2982 chitinase, acidic cpd 7f produced during type 2 inflammatory responses- allergic inflammation target MALT1 2983 MALT1 paracaspase pecazine target for severe autoimmune diseases FCGRT 2985 MHC class I-like Fc receptor, FcRn inhibitor- ARGX-113 (efgartigimod alfa); rozanolixizumab Phase 2 clinical candidate for myasthenia gravis (FDA orphan drug), pemphigus vulgaris and primary immune thrombocytopenia; Ph2 MG & primary immune thrombocytopenia ILDR2 2986 immunoglobulin like domain containing receptor 2 ILDR2-Fc ameliorates autoimmune diseases in rodent models (RA, MS) inhibitory immune checkpoint of B7 family MCAM 2988 melanoma cell adhesion molecule mAb PRX-003 implicated in the development of human autoimmune diseases FCAR 2991 Fc fragment of IgA receptor BsAb (CD89-CD20) bi-specific mAb that shows immuno-oncology potential STAT6 2993 signal transducer and activator of transcription 6 inhibitor- compound 19a [PMID: 26506089] role in IL-4 mediated biological responses- allergy and atopy STAT3 2994 signal transducer and activator of transcription 3 dual function TLR9 agonist-STAT3 inhibitor- CpG-STAT3dODN B cell lymphoma immunotherapy CD4 2995 CD4 molecule tregalizumab RA target; HIV target; T cell lymphoma target CYP5A1 1353 thromboxane A synthase 1 ozagrel anti-inflammatory target HPSE 2996 heparanase pixatimod immuno-oncology target GPR84 120 GPR84 surrogate agonists - 6-n-octylaminouracil and analogues eg PSB-17365 immuno-oncology target, anti-inflammatory target CD1D 2997 CD1d molecule AH10-7 immuno-oncology target, autoimmune disease target NRP1 2998 neuropilin 1 EG01377 immuno-oncology target, RA target NOX1 3001 NADPH oxidase 1 4 small mols incl GKT137831, GKT136901 anti-inflammatory target;esp NOX1/4 NOX4 3004 NADPH oxidase 4 4 small mols incl GKT137831, GKT136901 anti-inflammatory target TPBG 3009 trophoblast glycoprotein naptumomab estafenatox, anatumomab mafenatox immuno-oncology target CD37 3010 CD37 molecule lilotomab, naratuximab emtansine, otlertuzumab immuno-oncology target
  36. 36. New ligand > target example 36 first submitter
  37. 37. GtoImmuPdb ligands in PubChem for 2018.2 37 • Query “immunopharmacology” brings back 993 SIDs (817 Oct 2017) • Query AND “antibody” brings back 139 SIDs • From the 993 SIDs, 628 form small-molecule CIDs • Of the SIDs 258 are approved drugs
  38. 38. GtoImmuPdb > PubChem ligands > PubMed 38 ● Our 993 SIDs link to 2083 PMIDs (via our reference curation) ● Distribution of these by top-20 Journals shown below (More on Friday in :Linking GtoPdb <> PubChem <> PubMed from BPS journals: the power of more dot-joining)
  39. 39. Keep Calm and keep on curating… • Achievements outlined in slides report • Good progress leading up to beta release • Need committee/other expert inputs for • Triaging review articles • Dot joining/data mining on “big themes” (e.g. athero, glial cells in Alzheimer’s depression, immunometabolism etc) • How can we check if we have false-negative problem • Engage with key wet labs (e.g. for ligand testing in new systems) • Continue getting the word out (e.g. CIP press release) • Explore crowd-source options (e.g. an open call for papers) GtoImmuPdb achievements, issues, plans 39
  40. 40. Acknowledgements • All past and current members of NC-IUPHAR • NC-IUPHAR subcommittees and Concise Guide to PHARMACOLOGY contributors • Database team: • Jamie Davies (Principal Investigator) • Simon Harding and Joanna Sharman (Developers) • Adam Pawson, Elena Faccenda, Christopher Southan (Curators) • Tony Wigglesworth (Administrator) • All past and current NC-IUPHAR and web site sponsors • IUPHAR/BPS Guide to PHARMACOLOGY funders: 40
  41. 41. 41
  42. 42. ADDITIONAL SLIDES 42
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