Open PHACTS: meaningful linking of preclinical drug discovery knowledge

http://www.openphacts.org/

ACS 2013, New Orleans

Acknowledgements: Contains contributions from across the Open PHACTS partners.

#1 Introduction"To reduce the barriers to drug discovery in industry, academia and for small businesses, the Open PHACTS consortium is building an Open Pharmacological Space (OPS). This will be a freely available platform, integrating pharmacological data from a variety of information resources and providing tools and services to question this integrated data to support pharmacological research."

#1.1 Scientific questions

Example scientific questions

1. All oxido,reductase inhibitors active < 100 nM in both human and mouse.

2. Given a target find me all actives against that target. Find/predict polypharmacology of actives. Determine ADMET profile of actives.

3. Retrieve all experimental and clinical data for a given list of compounds defined by their chemical structure (with options to match stereochemistry or not).

4. Identify all known protein-protein interaction inhibitors.

#1.2 Architecture

Architecture: zooming in

Linking Data

http://www.openphacts.org/specs/datadesc/

Linking data: statistics

Ack: Alasdair, Christian (Manchester)

Units

WikiPathways

Pico, AR et al. PLoS biology 6.7 (2008): e184.

#1.3 Linked Data API

Example LDA call

REST-based

http://ops2.example.org/compound?uri=http%3A%2F%2Fwww.conceptwiki.org%2Fconcept%2F38932552-111f-4a4e-a46a-4ed1d7bdf9d5

... calls SPARQL

?ops_item skos:exactMatch ?cw_uri .?cw_uri skos:prefLabel ?compound_name ;

void:inDataset <http://www.conceptwiki.org> .?ops_item skos:exactMatch ?cs_uri .?cs_uri chemspider:smiles ?smiles ;

chemspider:inchi ?inchi ;chemspider:inchikey ?inchiKey ;ops:logp ?alogp ;ops:hba ?hba ;ops:hbd ?hbd ;ops:ro5_violations ?num_ro5_violations ;ops:psa ?psa;void:inDataset

<http://www.chemspider.com> .?ops_item skos:exactMatch ?equiv_compound . ?equiv_compound ?bNode1 ?molformula ;

?bNode2 ?molweight ;?bNode3 ?mw_freebase ;?bNode4 ?rtb ;void:inDataset

<http://data.kasabi.com/dataset/chembl-rdf>.?ops_item skos:exactMatch ?db_uri .

Open PHACTS timeline

• Explorer went open early 2013

• LDA goes open in 2013

• Open PHACTS (1) ends in 2014

Specifications (CC-BY-SA)

http://www.openphacts.org/specs/

Source code at (various Open licenses)

http://github.com/openphacts/

Data (mixed/open)

various locations

Conclusion & Thanx

● Joined effort of many partners

– I only have a small (1 FTE) role in this● Several partners around here at ACS

– Let me know if you like to meet any of them

● Details– http://www.openphacts.org/

– http://explorer.openphacts.org/

– Posters: http://www.openphacts.org/docs/173-posters

Associate Partner Program

Workshop in 2013