The document provides a status report on the Guide to Immunopharmacology database (GtoImmuPdb). It discusses developments including the addition of disease data, graphical browsing of cell type data, and process data. The database is in beta version 3 and undergoing user testing. Over 500 targets and 1,000 ligands have been curated from the literature. On the curation side, efforts are focused on expanding the literature collection and annotating new targets and ligands. The database is preparing for its official launch in October 2018.
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
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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
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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
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• Beta v3 (Now) > Full Release (Imminent) > Official Launch (Oct 2018)
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
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8. GtoImmuPdb Analytics
Google Analytics since July 2017
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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. GtoImmuPdb Data: Stats
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● 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. Disease Development
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● 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
13. Disease Categories
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● Categories will provide finding/browsing diseases easier
● Can have different categories for GtoImmuPdb / GtoPdb
● Use Disease Ontology to underpin categorisation
16. Disease Categories
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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
18. Disease Summary Pages
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Disease Summary page - Overview
Contain 3 sections: Overview, Targets and
Ligands
Top section - summarises association
data, give disease synonyms, description
and links
19. Disease Summary Pages
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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. Disease Summary Pages
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Disease Summary page - Target Ligands
Example of fezakinumab and IL-22
Some associations
with absent data
Target-ligand associations
not currently displayed
21. Disease Summary Pages
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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. Next steps – Disease
● Categorisation
● Implement disease name and synonym search
● Include target ligand associations in summary pages
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23. Cell Type Data
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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. Cell Type Data - Graphical Browse
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http://www.guidetoimmunopharmacology.org/GRAC/CelltypesForward
25. Process Data
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• 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. Process Data
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● Adjusted immuno process associations display
● IEA (Inferred by Electronic Annotation) hidden by default.
● “Assigned by automated methods, without curatorial judgement”
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”
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35. Target expansion
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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
37. GtoImmuPdb ligands in PubChem for 2018.2
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• 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. GtoImmuPdb > PubChem ligands > PubMed
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● 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. 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
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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:
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