DReNIn_O “A high-level ontology for drug repositioning” Joseph Mullen ICOS, School of Computing Science, Newcastle University Prof. Anil Wipat Dr. Simon Cockell Peter Woollard Brief introduction to the area of application- drug repositining. 1

“Increasing in cost and reducing in productivity” Drug Discovery “Increasing in cost and reducing in productivity” 2005-2009 22 drugs / year Low hanging fruit has been picked State of R&D needs to change Precision medicine or drug repositioning 19 year high of 45. Nearly half are for rare diseases. This increase in treatments for rare diseases has resulted in a slump of around 35% in average forecast sales between between 2014 and 2015 (US$1.4 bil- lion per 2014 drug and US$900 million per 2015 drug) [10], with rare diseases less rewarding, financially. Affect 6-7% of the worlds pop. < 200,000 in US 1 in 10,000 Due to economic incentives such as the FDA ODA.

“Identifying new uses for existing drugs” Drug Repositioning “Identifying new uses for existing drugs”

“Identifying new uses for existing drugs” Drug Repositioning “Identifying new uses for existing drugs” Marketed examples found due to ‘luck’ E.g. sildenafil (PAH -> ED) Need for more systematic approaches Such as systems approaches

“Enables an holistic view of a drugs interactions” Systems Approach “Enables an holistic view of a drugs interactions” DRUG TARGET DISEASE binds to Involved in has indication Systems approaches, in particular, provide a method of utilising this data increase, and can ac- cumulate evidence supporting discovery of new uses or indications of existing drugs. systems biology approach promises to fulfil the need for a systematic approach to drug repositioning by utilising an integrated view of cellular and molecular processes. This approach provides a complementary path to re- ductionist science in understanding complex phenomena. Data integration is an essential part of a systems biology approach, since it allows for the integrative analysis of multiple data sources Requires data integration and data mining

“Allows for a holistic view of a drugs interactions” Systems Approach “Allows for a holistic view of a drugs interactions” Clinical Trial Small Molecule Pathway GO MoA Rare Disease Bio Tech Common Disease DRUG TARGET DISEASE Drug Combination binds to Involved in Nutraceutical has indication Systems approaches, in particular, provide a method of utilising this data increase, and can ac- cumulate evidence supporting discovery of new uses or indications of existing drugs. systems biology approach promises to fulfil the need for a systematic approach to drug repositioning by utilising an integrated view of cellular and molecular processes. This approach provides a complementary path to re- ductionist science in understanding complex phenomena. Data integration is an essential part of a systems biology approach, since it allows for the integrative analysis of multiple data sources Requires data integration and data mining Gene Protein Binding site Alternative Transcript Isoform

“A high-level ontology for drug repositioning” DReNIn_O “A high-level ontology for drug repositioning” Biological and pharmacological entities as well as annotation and data to be used to validate any inferences made. https://bitbucket.org/ncl-intbio/drenin_ontology

“An RDF drug repositioning dataset with a SPARQL endpoint” DReNIn “An RDF drug repositioning dataset with a SPARQL endpoint” 8 million triples. Allows us to ask questions that cannot be answered by other http://drenin.ncl.ac.uk

To Conclude DReNIn_O high level ontology Systems approaches to drug repositioning Data integration Data mining Infer novel uses for existing drugs

We thank the EPSRC and GSK for funding of the CASE studentship. Acknowledgements Prof. Anil Wipat and Dr. Simon Cockell from Newcastle University. Dr. Philipe Sanseau, Peter Woollard and Hannah Tipney from GSK. We thank the EPSRC and GSK for funding of the CASE studentship.

j.mullen@ncl.ac.uk QUESTIONS?