The path through drug discovery is lengthy, costly and characterised by low success rates, with many potential drugs failing due to lack of safety or efficacy. Generating and interpreting the data required to identify a good drug target demands a diverse set of skills, evidence types and technologies, which rarely exist today in any single organisation. Open Targets brings expertise from EMBL-EBI and the Wellcome Sanger Institute, and five pharmaceutical companies (Biogen, Celgene, GSK, Sanofi, and Takeda) to systematically identify and prioritise targets from which safe and effective medicines can be developed. In this talk, I will highlight the work we are carrying out in two major areas of research in Open Targets, data generation and data integration, through a portfolio of experimental and bioinformatics projects. We are committed to openly sharing our data with the scientific community through publications and Open Targets web resources, such as the Open Targets Platform and Open Targets Genetics

1. Open Targets: identifying drug
targets in a pre-competitive
framework
Denise Carvalho-Silva, PhD
EMBL-EBI | Open Targets
Wellcome Genome Campus
United Kingdom
BSPR meeting 2019
July 2nd 2019

2. Acknowledgements

3. MYOC - glaucoma
(PDBe 4wxs)
Most drug targets are proteins
SNCA - Parkinson’s
(PDBe 6rt0)
Genetic variants  protein structure  diseases

4. Selecting the right target
Drug discovery is challenging

5. Open Targets
A partnership to transform drug discovery
Founded in 2014
Founding partners 2016 2017 20182018
Systematic identification and prioritisation of targets

6. DATA
GENERATION
Therapeutic
hypothesis
Public data
DATA
INTEGRATION
Experimental projects Bioinformatics projects
Knowledge cycle

7. Data integration: Open TargetsData integration: informatics
https://www.targetvalidation.org https://genetics.opentargets.org

8. Target
(protein and non-protein coding genes)
Disease
(rare and common)
Evidence
(variants, drugs, literature, etc)
https://www.targetvalidation.org
Open Targets Platform: data model

9. Filter by
data types Diseases associated with MYOC
from two therapeutic areas
Associations for a target
Is my protein associated with a disease?

10. Is my target expressed in the relevant
tissue?

11. Is my target tractable?
DOI:10.1517/17460441.3.4.391
https://www.immunology.org/structure-antibody-1972

12. Is my target safe to be modulated?
193 proteins with safety information
• Drowsiness
• Increased heart rate
• Hepatotoxicity

13. Target prioritisation
Target profile

14. MYOC - glaucoma
(PDBe 4wxs)
What is the protein function in health?
SNCA - Parkinson’s
(PDBe 6rt0)
EMBL-EBI protein resources and Open Targets collaboration

15. PepVEP
• Integrated framework to deliver functional information per AA
• Mapping to clinical and disease associations

16. • Resource of integrated multiomics data
• Target identification and prioritisation
• Graphical web interface: easy to use
• REST-API for larger, more flexible queries
June 2019 release, 19.06
Open Targets Platform
27K
targets
10K
diseases
3.3 M
associations
7.2 M
evidence

17. Where to find out more?

18. DATA
GENERATION
Therapeutic
hypothesis
Public data
DATA
INTEGRATION
Experimental projects Bioinformatics projects
Knowledge cycle
https://www.targetvalidation.org
https://genetics.opentargets.org

19. Data generation: therapeutic areas
9 ongoing projects
5 ongoing projects
3 complete projects
1 publication (2019)1 publication (2019)
3 manuscripts on bioRxiv
2 complete projects
7 ongoing projects

20. Prioritising targets and pathways
Behan et al. 2019
Vieira-Braga et al. 2019

21. Open Targets community
blog.opentargets.org/
@targetvalidate
http://tinyurl.com/opentargets-in
https://tinyurl.com/opentargets-youtube
Thank you!