What has Open PHACTS done so far? Lee Harland On behalf of the Open PHACTS Consortium

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1 What has Open PHACTS done so far? Lee Harland On behalf of the Open PHACTS Consortium

2 Pre-competitive Informatics: Pharma are all accessing, processing, storing & re-processing external research data Literature Patents PubChem Genbank Databases Downloads x each company Data Integration Data Analysis Firewalled Databases Lowering industry firewalls: pre-competitive informatics in drug discovery Nature Reviews Drug Discovery (2009) 8, doi: /nrd2944

3 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

4 The Mission A shared infrastructure for data integration; promoting best practice and facilitating collaboration Stable API For Science & Apps Use & Develop Standards Solve Key Use Cases Synergy Across Industry

5 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

6 So We Built A Team 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 Spanish National Cancer Research Centre University of Manchester Maastricht University Aqnowledge University of Santiago de Compostela Rheinische Friedrich-Wilhelms-Universität Bonn AstraZeneca GlaxoSmithKline Esteve Novartis Merck Serono H. Lundbeck A/S Eli Lilly Netherlands Bioinformatics Centre Swiss Institute of Bioinformatics ConnectedDiscovery EMBL-European Bioinformatics Institute Janssen OpenLink pmu@openphacts.org

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8 Much knowledge transfer between people with strong track records in these areas between academic partners and industry, and across industry participants

9 Business Question Driven Approach Number sum Nr of 1 Question All oxidoreductase inhibitors active <100nM in both human and mouse 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? Given a target find me all actives against that target. Find/predict polypharmacology of actives. Determine ADMET profile of actives For a given interaction profile, give me compounds similar to it 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. 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

10 Mechanism for prioritisation, selection, testing, use-case validation

11 The Open PHACTS Discovery Platform

12 An Open Platform

13 Something you can build on

14 Something you can use!

15 Dealing With The Tough Parts

16 Dealing With The Really Tough Parts John Wilbanks Data Licensing Solution

17 Data Confidence & Validation ChemSpider Validation & Standardization Platform

18 Promoting Standards

19 Provenance Everywhere

20 Enhancing The SW Ecosystem ApiNATOMY Bridge Db ChEMBL Chemical Validation and Standardization Platform (CVSP) ConceptWiki Dataset Descriptors DisGeNET Identifiers.org Identity Mapping System (IMS) jqudt Linked Data Benchmark Council nextprot Utopia W3C-PROV Ontology WikiPathways

21 A Community

22 Assisting Users

23 What has Open PHACTS done so far? Created a viable shared infrastructure for data integration Created a methodology for delivery of business-relevant solutions Established itself within the wider community and facilitated idea exchange and collaboration But there is still a lot to do.

24 Future Possibilities Open PHACTS to go deployable package/vm Increase data content (genetics, clinical, expression, biomarkers) Form alliances to generate new (missing) content in the public domain Value Add scientific services Your ideas..

25 Acknowledgements 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 Spanish National Cancer Research Centre University of Manchester Maastricht University Aqnowledge University of Santiago de Compostela Rheinische Friedrich-Wilhelms-Universität Bonn AstraZeneca GlaxoSmithKline Esteve Novartis Merck Serono H. Lundbeck A/S Eli Lilly Netherlands Bioinformatics Centre Swiss Institute of Bioinformatics ConnectedDiscovery EMBL-European Bioinformatics Institute Janssen OpenLink