title: The application of the open pharmacological concepts triple store (open PHACTS) to support drug discovery research.
abstract: Integration of open access, curated, high-quality information from multiple disciplines in the Life and Biomedical Sciences provides a holistic understanding of the domain. Additionally, the effective linking of diverse data sources can unearth hidden relationships and guide potential research strategies. However, given the lack of consistency between descriptors and identifiers used in different resources and the absence of a simple mechanism to link them, gathering and combining relevant, comprehensive information from diverse databases remains a challenge. The Open Pharmacological Concepts Triple Store (Open PHACTS) is an Innovative Medicines Initiative project that uses semantic web technology approaches to enable scientists to easily access and process data from multiple sources to solve real-world drug discovery problems. The project draws together sources of publicly-available pharmacological, physicochemical and biomolecular data, represents it in a stable infrastructure and provides well-defined information exploration and retrieval methods. Here, we highlight the utility of this platform in conjunction with workflow tools to solve pharmacological research questions that require interoperability between target, compound, and pathway data. Use cases presented herein cover 1) the comprehensive identification of chemical matter for a dopamine receptor drug discovery program 2) the identification of compounds active against all targets in the Epidermal growth factor receptor (ErbB) signaling pathway that have a relevance to disease and 3) the evaluation of established targets in the Vitamin D metabolism pathway to aid novel Vitamin D analogue design. The example workflows presented illustrate how the Open PHACTS Discovery Platform can be used to exploit existing knowledge and generate new hypotheses in the process of drug discovery.
authors.affiliation: Universidade de Santiago de Compostela, Grupo BioFarma-USEF, Departamento de Farmacología, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Joseline
authors.initials: J
authors.lastname: Ratnam
authors.affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zdrazil
authors.affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Digles
authors.affiliation: Universidade de Santiago de Compostela, Grupo BioFarma-USEF, Departamento de Farmacología, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Cuadrado-Rodriguez
authors.affiliation: Janssen Research & Development, Turnhoutseweg 30, Beerse, Belgium.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Neefs
authors.affiliation: GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Tipney
authors.affiliation: Vrije Universiteit, Faculty of Sciences, division of Math. and Computer Science, De Boelelaan 1081a, 1081 HV Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Siebes
authors.affiliation: Department of Bioinformatics - BiGCaT, Maastricht University, Maastricht, The Netherlands.
authors.forename: Andra
authors.initials: A
authors.lastname: Waagmeester
authors.affiliation: GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, United Kingdom.
authors.forename: Glyn
authors.initials: G
authors.lastname: Bradley
authors.affiliation: GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, United Kingdom.
authors.forename: Chau Han
authors.initials: CH
authors.lastname: Chau
authors.affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Lars
authors.initials: L
authors.lastname: Richter
authors.affiliation: Universidade de Santiago de Compostela, Grupo BioFarma-USEF, Departamento de Farmacología, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Brea
authors.affiliation: Department of Bioinformatics - BiGCaT, Maastricht University, Maastricht, The Netherlands.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Evelo
authors.affiliation: Janssen Research & Development, Turnhoutseweg 30, Beerse, Belgium.
authors.forename: Edgar
authors.initials: E
authors.lastname: Jacoby
authors.affiliation: GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Senger
authors.affiliation: Universidade de Santiago de Compostela, Grupo BioFarma-USEF, Departamento de Farmacología, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Loza
authors.affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Gerhard F
authors.initials: GF
authors.lastname: Ecker
authors.affiliation: Swiss Institute of Bioinformatics, CALIPHO Group, CMU - Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Chichester
mesh_terms: D019992:Databases as Topic; D055808:Drug Discovery / Q000379:methods / Q000458:organization & administration* / Q000706:statistics & numerical data; D012984:Software