This document discusses integrating the Open PHACTS knowledgebase with Pipeline Pilot software to answer research questions. Open PHACTS is a public-private partnership focused on key problems in drug discovery like efficacy and safety. It creates a semantic integration hub with linked data from various sources. The document outlines partnerships, datasets integrated, and the API. It describes a hackathon to demonstrate querying Open PHACTS via Pipeline Pilot components, enabling drag-and-drop workflow creation. Examples show answering questions on bioactivity data for molecules matching a substructure. Components were developed to map API calls in Pipeline Pilot. Addressing the hierarchical Open PHACTS data structure remains a challenge.

1. Adressing Research Questions by Integration
of Open PHACTS with Pipeline Pilot
Accelrys Seminar, Mainz, 14th May 2013
Christian Herhaus, Global Computational Chemistry

2. Innovative Medicines Initiative
•
•
2
EC funded public-private partnership
for pharmaceutical research
Focus on key problems
– Efficacy, Safety,
– Education & Training,
– Knowledge Management
The Open PHACTS Project
• Runs 2011-2014
• Create a semantic integration hub
(“Open Pharmacological Space”)
• Deliver services to support ongoing drug discovery programs in
pharma and public domain
• Leading academics in semantics,
pharmacology and informatics,
• Driven by solid industry business
requirements
http://www.openphacts.org/

3. Open PHACTS Partners
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4. Associate Partners
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5. Focused on Answering Business Questions
“What is the
selectivity profile of
known p38 inhibitors?”
“Find compounds which
hit most specifically
the multiple targets in
a given pathway”
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“Let me compare
MW, logP and PSA
for known
oxidoreductase
inhibitors”
“Find me compounds
that inhibit targets
in NFkB pathway
assayed in only
functional assays
with a potency <1 μM”
“For a given
interaction profile,
give me compounds
similar to it.”

6. Datasets and Links
815 millions of Data triples, 18 millions of Mapping triples
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7. Platform
Architecture
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8. The Open PHACTS Linked Data API
https://dev.openphacts.org/
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9. Pipeline Pilot Hackathon
Cambridge, 20th Feb 2013
• Demonstrate that the integration of the Open PHACTS API and
Pipeline Pilot (PP) is possible
• Create a library of PP components for the Open PHACTS API
• Enable:
Easy querying of the Open PHACTS API
“Drag and drop” creation of useful PP workflows
Customisation of PP components
PP component transparency
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10. Connecting to Open PHACTS with PPilot
Example URL:
https://$(ops_server)/structure/similarity?app_id=$(app_id)&app_key=$(app_key)
&searchOptions.Molecule=c1ccccn1&searchOptions.SimilarityType=0
&searchOptions.Threshold=0.7&_format=json
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11. Answering Questions: Hackathon Example
"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".
Substructure SMILES
ChemSpider URI
ConceptWiki URI
Enzyme class
members
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+
Pharmacology
information
Pharmacology information for
desired assay of molecules with
substructure

12. By Chris Chau (GSK)
Pathway
information
Entrez
ID
Example Results:
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Biomart web
service
Uniprot
IDs
Conceptwiki
mapping
Target
URIs
Target by
pharmacology
Results
Filter by EC50

13. From Tailored Prototyping to a Toolbox
Modularisation of partial solutions along Open PHACTS API calls
OUTPUT
ISIS/Draw
Sketcher
Molecule from
SMILES
Similarity search
INPUT
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Viewer

14. Mapping API Calls to Components
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15. Open PHACTS Hierarchical Data Structure
A Challenge for Pipeline Pilot Data Tree Functionality
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16. Unfolding the Open PHACTS Data Hierarchy
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17. Thank you!
Slides:
• Lee Harland (Connected Discovery Ltd.)
• Jack Gibb (Royal Society of Chemistry)
• Chris Chau (GlaxoSmithKline)
• … and many other authors from EFPIA and Open PHACTS
Administration:
• Stefan Senger (GlaxoSmithKline)
• Noj Malcolm (Accelrys)
Merck Serono:
• Thomas Grombacher
• Oliver Karch
• Friedrich Rippmann
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