Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery
The Open Targets Platform is a unique, open-source, publicly-available knowledge base providing data and tooling for systematic drug target identification, annotation, and prioritisation. We have expanded the scope of the Platform through significant enhancements and data updates to enable users to formulate more flexible and impactful therapeutic hypotheses.
Enhancements and Updates
We have revamped our target–disease associations page with more interactive facets and built-in functionalities to empower users with additional control over their experience. A new Target Prioritisation view allows users to prioritize targets based on clinical precedence, tractability, doability, and safety attributes. We have also implemented a direction of effect assessment for eight sources of target–disease association evidence, showing the effect of genetic variation on the function of a target associated with risk or protection for a trait.
These enhancements and the introduction of new back and front-end technologies have increased the impact and usability of our resource within the drug discovery community.
Challenges in Drug Discovery
Our ability to develop safe and effective medicines is limited by an incomplete understanding of disease biology. Enhancing the understanding of disease-causal mechanisms at the target discovery stage can significantly improve success rates and reduce early stoppage of clinical studies. However, the information required to formulate precise therapeutic hypotheses is often sparse.
Several resources have attempted to consolidate publicly available information into web services to assist in the identification of drug targets, but the challenge remains in converting data into actionable knowledge.
Open Targets Platform
The Open Targets partnership combines expertise from academia and the pharmaceutical industry to support the systematic identification and prioritisation of drug targets. The Open Targets Platform is the flagship resource of this partnership, providing open-source data and informatics tools for the scientific community.
Data Integration and Prioritisation
The Platform integrates data from 23 independent public sources to establish causal links between drug targets and indications. Targets and diseases are mapped to Ensembl gene identifiers and Experimental Factor Ontology terms, with evidence scored and aggregated to build a ranked list of associations summarising confidence in the causal relationship.
Genetic variations associated with diseases can be leveraged to identify novel drug targets. The Platform systematically integrates human germline and somatic genetic variation data associated with diseases for target prioritisation.
Recent Updates
The Platform has expanded its understanding of common disease genetics through the inclusion of the latest Open Targets Genetics post-genome-wide association studies (GWAS) analysis data release. Updates include the incorporation of splicing QTLs from GTEx version 8 and the expansion of GWAS/molecular trait colocalisation results.
Interpreting rare protein-coding events complements GWAS analysis in depicting the genetic architecture of common conditions. Recent updates include the curation of Gene Burden results from large-scale cohort studies and evidence informing about circulating metabolic biomarkers for cardiovascular disease.
