Open PHACTS for Academia
The Open PHACTS
Discovery Platform
Patent
Expiry
Generic
Competition
PwC - Pharma 2020 – Which Path will you take
http://www.rsc.org/chemistryworld/Issues/2009/January/PharmaRefocusesOnThePatent
Cliff.asp
Cost
Containment
$1.4
$1.3B
$1.2
$1.0
$0.8
$800M
$0.6
$0.4
$300M
$0.2
$100M
$0.0
1979
1991
2000
2005
Improve
R&D
Productivity
Public Domain Drug Discovery Data:
Pharma are accessing, processing, storing & re-processing
Literature Genbank
Patents PubChem
Data Integration
Databases
Data Analysis
Downloads
Firewalled Databases
We are all doing this many times……
Merck-Serono
Novartis
Roche
AstraZeneca
Pfizer
GSK
Over the last decade
• Data has become more open
• Data has become better represented (Standards)
• Major providers are becoming more organised (NCBI, EBI, FDA)
BUT
Integration across sources, and across providers is
still a gap
Pre-competitive Informatics:
Pharma are all accessing, processing, storing & re-processing external research data
Literature Genbank
Patents PubChem
Data Integration
Databases
Data Analysis
Downloads
x
Repeat @
each
company
Firewalled Databases
Lowering industry firewalls: pre-competitive informatics in drug discovery
Nature Reviews Drug Discovery (2009) 8, 701-708 doi:10.1038/nrd2944
The Innovative Medicines Initiative
• EC funded publicprivate partnership for
pharmaceutical
research
• Focus on key problems
– Efficacy, Safety,
Education &
Training,
Knowledge
Management
The Open PHACTS Project
• Create a semantic integration hub (“Open
Pharmacological Space”)…
• Runs 2011-2014, ENSO till 2016
• Deliver services to support on-going drug
discovery programs in pharma and public domain
• Leading academics in semantics, pharmacology
and informatics, driven by solid industry business
requirements
• 31 academic partners, 9 pharmaceutical
companies, 3 software SMEs
• Work split into clusters:
• Technical Build
• Scientific Drive
• Community & Sustainability
Open PHACTS Mission:
Integrate Multiple Research
Biomedical Data Resources
Into A Single Open & Free
Access Point
The Real Mission
Starting from a relatively blank canvas, build a pharmacology-centric
integration system that’s as good as, or better than, that which pharma
already have after decades of working in this space….
…with a distributed set of people who have never met and many of which
have not worked on drug-discovery previously…
…using an emerging, actively evolving technology…
…with an architecture that fulfils the need of both public and private
users…
…in just over a couple of years…
…whilst doing some research at the same time
“Let me compare
MW, logP and PSA
for known
oxidoreductase
inhibitors”
“What is the
selectivity profile of
known p38 inhibitors?”
ChEMBL
ChEBI
DrugBank
UniProt
ConceptWiki
Gene
Ontology
“Find me compounds
that inhibit targets in
NFkB pathway assayed
in only functional assays
with a potency <1 μM”
Wikipathways
UMLS
ChemSpider
GeneGo
GVKBio
TrialTrove
TR Integrity
Business Question Driven Approach
Number
15
sum
12
Nr of 1
9
Question
18
14
8
Given compound X, what is its predicted secondary pharmacology? What are the on and
off,target safety concerns for a compound? What is the evidence and how reliable is that
evidence (journal impact factor, KOL) for findings associated with a compound?
24
13
8
Given a target find me all actives against that target. Find/predict polypharmacology of actives.
Determine ADMET profile of actives.
32
13
8
For a given interaction profile, give me compounds similar to it.
37
13
8
The current Factor Xa lead series is characterised by substructure X. Retrieve all bioactivity data
in serine protease assays for molecules that contain substructure X.
38
13
8
41
13
8
44
13
8
46
13
8
59
14
8
All oxidoreductase inhibitors active <100nM in both human and mouse
Retrieve all experimental and clinical data for a given list of compounds defined by their chemical
structure (with options to match stereochemistry or not).
A project is considering Protein Kinase C Alpha (PRKCA) as a target. What are all the
compounds known to modulate the target directly? What are the compounds that may modulate
the target directly? i.e. return all cmpds active in assays where the resolution is at least at the
level of the target family (i.e. PKC) both from structured assay databases and the literature.
Give me all active compounds on a given target with the relevant assay data
Give me the compound(s) which hit most specifically the multiple targets in a given pathway
(disease)
Identify all known protein-protein interaction inhibitors
The Open PHACTS Discovery Platform
• Cloud-Based
“Production” Level
System. Secure & Private
• Guided By Business
Questions
http://dx.doi.org/10.1016/j.drudis.2013.05.008
• Uses Semantic Web
Technology But provides
a simple REST-ful API for
everyone else
http://dx.doi.org/10.1016/j.websem.2014.03.003
http://imgs.xkcd.com/comics/standards.png
Basic Semantic web standards
– SPARQL 1.1, RDF(S), SKOS
Dataset descriptions
– Vocabulary of Interlinked Datasets (VoID)
– VoID linkset descriptions
QUDT Quantities, Units, Dimensions and Types
Provenance
– W3C PROV, PAV, Nanopublications
BioPortal, ConceptWiki, ChEMBL, identifiers.org,
Uniprot, ChemSpider
Are These Two Molecules The Same(*)
Yeah
No
way!
*Really: Is it sensible to combine data associated with these two molecules?
Data Licensing Solution
Chose John Wilbanks as consultant
A framework built around STANDARD well-understood
Creative Commons licences – and how they interoperate
Deal with the problems by:
Interoperable licences
Appropriate terms
Declare expectations to users and
data publishers
One size won‘t fit all requirements
Kick-Starting Sustainability
Apps
API Users
Collaboration
Grants
Industry
Open PHACTS
API
Open PHACTS Associate
Partner Community
Leveraging Our Community
Associated partners
MoU
Organisations, most will join here
Support, information
Exchange of ideas, data, technology
Opportunities to demo at community webinars
Need MoU
Development partnerships
Influence on API developments
Opportunities to demo ideas & use cases to core team
Need MoU and annexe
Consortium
31 current members
Associated
partners
+Annexe
Development
partnerships
Consortium
Open PHACTS Mission:
Integrate Multiple Research
Biomedical Data Resources
Into A Single Open & Free
Access Point
Sustaining Impact
“Software is free like
puppies are free they both need
money for
maintenance”
…and more resource
for future
development
M embership
Benefits
Integrated data:
Pharmacological
Physicochemical
The not-for-profit Foundation maintains the Open PHACTS Discovery Platform, a
versatile infrastructure of integrated biomedical data, and actively engages an ecosystem
of industry and academic semantic web experts.
Steer the direction
Prioritise new projects
Get involved with Foundation governance
Identify development opportunities
Propose new data sources to include
Develop new use-cases and workflows
P
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M embership Levels
Disease
Gene
Pathways
Training opportunities
Engage a community of
Enjoy training opportunities by experts.
experts and peers
The Foundation serves a unique and vibrant
Early access to releases
scientific community, facilitating collaboration
Members have early access to infrastructure
between the pharma industry, academia & SMEs.
and platform updates and new releases,
including a locally installable system
Fe
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Influence the security policy
www.openphactsfoundation.org
turnover. Pay in cash or by donating
Full
Nominate and vote for
people-hours to the Foundation.
[email protected]
the Board of Trustees
Contributing
Individual
Vote for the Board
of Trustees
Non-voting
Get involved in projects
and collaborate
Open PHACTS Foundation
c/ o Royal Society of Chemistry,
Thomas Graham House,
Science Park, Cambridge, CB4 0WF
Compa
nynumbe
r854829
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[email protected]
Acknowledgements
Open PHACTS Practical Semantics
[email protected]
@Open_PHACTS
Pfizer Limited – Coordinator
Universität Wien – Managing entity
Technical University of Denmark
University of Hamburg, Center for
Bioinformatics
BioSolveIT GmBH
Consorci Mar Parc de Salut de Barcelona
Leiden University Medical Centre
Royal Society of Chemistry
Vrije Universiteit Amsterdam
Novartis
Merck Serono
H. Lundbeck A/S
Eli Lilly
Netherlands Bioinformatics Centre
Swiss Institute of Bioinformatics
ConnectedDiscovery
EMBL-European Bioinformatics Institute
Janssen
Esteve
Almirall
OpenLink Scibite
The Open PHACTS Foundation
Spanish National Cancer Research Centre
University of Manchester
Maastricht University
Aqnowledge
University of Santiago de Compostela
Rheinische Friedrich-Wilhelms-Universität
Bonn
AstraZeneca
GlaxoSmithKline