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.
Highlights
While the approval rates for new drugs may be somewhat stable, pharmacological data of increasing size, dimensionality and complexity is being housed in public and proprietary databases [1], [2]
Use case A assembled a ranked list of compounds targeting the dopamine receptor D2 (DRD2) and found related targets in both public and proprietary pharmacology databases to aid in the design of a new compound library for the dopamine receptor drug discovery program
Use case C evaluated established targets in the Vitamin D metabolism pathway and expanded the scenario to view these targets in other contexts
Summary
While the approval rates for new drugs may be somewhat stable, pharmacological data of increasing size, dimensionality and complexity is being housed in public and proprietary databases [1], [2] Within these separate data pools resides valuable scientific information that can help in the design of novel drugs, for example by predicting protein interactions with novel compounds [3], [4], [5], suggesting novel molecules with better properties or by finding existing chemical matter to test against a newly identified target. An integrated and comprehensive interface to publicly available pharmacology, physicochemical and biomolecular data could support initial drug screening stages and limit expensive late-stage trial failure. Such tools would be invaluable to academia and small to medium enterprises (SMEs), which have historically enjoyed little access to proprietary integrated platforms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
