Open Targets: Mining gene and disease associations for improved drug target identification

Part of EMBL-EBI webinar seriesOctober 18th 2017

The logistics for the next hour

• 

•  switch to desktop version

•  ‘Materials’ section: presentation.pdf

•  muted

•  Take questions at the end: look for the chat box!

•  Evaluation survey

Chat box

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What is the Open Targets Platform?

How to navigate the Platform?

Goals

What is the Open TargetsConsortium?

Outline

•  Introduction

•  Live demos

•  Wrap up

Outline

•  Introduction

•  Live demos

•  Wrap up

Drug discovery path: timeline

Source: doi:10.1038/nrd1470

Lengthy, costly, low success rate, HIGH ATTRITION RATES

Drug discovery: the challenges

Our Vision

A partnership to transform drug discovery through the systematic identification and

prioritisation of targets

Causal links between

targets and disease

Support data driven prioritisation

decision making Share tools

and methods for

target ID

Change attrition rates of industry pipelines

Publish high impact

science, and openly share our

data

World leader for human target discovery

Two major areas of work in Open Targets

Core bioinformatics pipelines

www.opentargets.org/projects

Experimental projects

Integration of available dataWeb interface

REST API Data dumps

Generate new evidenceCRISPR/Cas9

Organoids and IPS cells(cellular models for disease)

Concurrent

Core bioinformatics pipelines

www.opentargets.org/projects

Experimental projects

Concurrent

Two major areas of work in Open Targets

Generate new evidenceCRISPR/Cas9

Organoids and IPS cells(cellular models for disease)

Integration of available dataWeb interface

REST API Data dumps

Open Targets Platform*

•  Developed by the Core team at EMBL-EBI

•  To allow users to identify target and disease associations

•  Improvements driven by you

* First release: December 2015

Experimental Factor Ontology (EFO)

•  Ontology: dictionary of relationships between entities

•  EFO: way to organise experimental variables (e.g. diseases)

Promotes consistencyIncreases the richness of annotationAllow for easier and automatic integration

controlled vocabulary +

hierarchy (relationship)

Evidence model

Original sources à more being added

Evidence from publicly available data

targetvalidation.org/data_sources

Data integration

Data generation

OncologyImmunology

Neurodegeneration

OpenTargets Platform

Present and Future

Generated as we speak

EVA!

UniProt!

Gene2Phenotype!

GWAS catalog!

Cancer Gene Census!

EVA (somatic)!

IntOGen!

ChEMBL!

Reactome!

Expression Atlas!

Europe PMC!

PhenoDigm!!

Genetic associations!

Somatic mutations!

RNA expression!

Animal models!

Affected pathways!

Text mining!

Drugs!

*1.0!

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*0.5!

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*0.2!

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Association!

S1 + S2/22 + S3/32 + S4/42 + Si/i2

ΣH

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Genomics England!

PhEWAS catalog!*1.0!

*1.0!ΣH

ΣH

How do we score the associations?

Calculated at 4 levels:

•  Evidence•  Data source•  Data type•  Overall

Score: 0 to 1 (max)

weight factor

Aggregation with (harmonic sum)

ΣHNote: Each data set has

its own scoring and ranking scheme

Outline

•  Introduction

•  Live demos

•  Wrap up

Which targets are associated with a disease?

https://www.targetvalidation.org/

Demo 1: Disease centric workflow

*Supported ones: Internet Explorer 11 (and above), Chrome, Firefox and Safari

Choose your favourite internet browser*

What is the evidence for the association between CD86

and multiple sclerosis?

https://www.targetvalidation.org/evidence/ENSG00000114013/EFO_0003885

Demo 2: Evidence for an association

Target profile page

Disease profile page

We have a list of 26 possible targets for IBD (inflammatory

bowel disease).

https://www.targetvalidation.org/batch-search

Demo 3: Several targets at once

Are these targets represented in other diseases?

Which pathways are represented in this set of

targets?

Alternative ways to access the data

Outline

•  Introduction

•  Live demos

•  Wrap up

DataGenera)on

Therapeu)cHypothesis

PublicData

DataIntegra)on

targetvalidation.org

Experimental Projects Bioinformatic Projects

Wrap up

For drug target ID and selection in drug discoveryRank target and disease associations: different sourcesIntegrated information on target and diseases

Intuitive graphical web interface

June 2017 release

26Ktargets

9.1Kdiseases

2.8 Massociations

5.3 Mevidence

Open Targets Platform

We support decision-makingWhich targets are associated with a

disease?

Are there FDA drugs for this association?

…

Can I find out about the mechanisms of the

disease?

How to cite us

http://nar.oxfordjournals.org/content/45/D1/D985.long

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Acknowledgements

blog.opentargets.org/

@targetvalidate

www.facebook.com/OpenTargets/

support@targetvalidation.org

http://tinyurl.com/opentargets-in

Support, dissemination, video tutorials

http://imgur.com/a/JIDCPhttp://imgur.com/a/LKDhp

https://vimeo.com/233638392

Upcoming EMBL-EBI webinarshttp://www.ebi.ac.uk/training/webinars

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