A comprehensive understanding of the full target space of bioactive substances, including approved and investigational drugs, as well as chemical probes, provides important insights into therapeutic and biological potential and liabilities. In recent years, multiple resources have been developed based on diverse compound collections with the aim to define primary targets of small molecules and to identify potent molecular probes for specific molecular targets. While these resources have been useful for phenotypic profiling and drug development efforts, they provide limited annotation of the assays that generated the data. Such assay information is essential for end-users to understand and sort out variability in the bioactivity data. Moreover, existing data curation is largely being done in a closed manner, lacking an open and transparent platform that would allow community-level participation.
The DTC research team believes that the challenge of bioactivity annotation and curation should be addressed jointly by the whole research community. To enable such a collective effort, they implemented Drug Target Commons, a community-based, crowdsourcing initiative designed to improve the consensus and wider use of drug-target bioactivity data for drug discovery, target identification and drug repurposing applications. The web-based DTC platform aims to standardize the collection, management, curation and annotation of the notoriously heterogeneous compound-target bioactivity measurements, with the goal to provide the most comprehensive, reproducible and sustainable bioactivity knowledgebase for end-users.
“High quality bioactivity data will be supplemented by DTC at the proteome-scale based on crowd-sourced curation. It also opens up the opportunity to develop new tools and applications. In the future, we plan to integrate new web-based modules into DTC which will provide further insights on molecules and biologicals”, says the DTC lead developer Dr. Zia-ur-Rehman Tanoli.
The DTC effort is open to anyone who would like to contribute to the open-data sharing, curation and annotation process, under the Creative Commons Licence, including academic partners and pharmaceutical and biotechnology companies.
“DTC is a beautiful example of open science and how local and global teams of researchers can provide harmonized resources out of existing data to foster data reuse and drug repurposing opportunities”, says Gretchen Repasky, Senior Researcher at FIMM.
As the DTC community grows, the long-term value of the DTC platform expands, as bioactivity data from newly-published studies will be continuously uploaded to DTC by the user community and subjected to the annotation process by the community of domain experts. In doing so, the community effort will expand our knowledge and use of compound bioactivity profiles in both academic and industrial applications.
“To understand the mechanisms of drugs in different biological systems, we need a database that contains the affinity and activity of all drugs against all possible targets. DTC is a fantastic way to engage the scientific community in laying the groundwork for such a database. DTC holds enormous potential for drug classification, combination design, repurposing and data accessibility,” says Markus Vähä-Koskela, Senior Researcher at FIMM
Jing Tang , Zia-ur-Rehman Tanoli, Balaguru Ravikumar, Zaid Alam , Anni Rebane, Markus Vähä-Koskela, Gopal Peddinti, Arjan J. van Adrichem, Janica Wakkinen, Alok Jaiswal, Ella Karjalainen, Prson Gautam, Liye He, Elina Parri, Suleiman Khan, Abhishekh Gupta, Mehreen Ali, Laxman Yetukuri, Anna-Lena Gustavsson , Brinton Seashore-Ludlow, Anne Hersey, Andrew R. Leach, John P. Overington, Gretchen Repasky, Krister Wennerberg, and Tero Aittokallio. DrugTargetCommons – A community effort to build a consensus knowledgebase for drug-target interactions. Cell Chemical Biology 2017. DOI: http://dx.doi.org/10.1016/j.chembiol.2017.11.009
Jing Tang, PhD, Group Leader, Jing.firstname.lastname@example.org
Krister Wennerberg, PhD, Prof., FIMM-EMBL Group Leader, email@example.com
Tero Aittokallio, PhD, Prof., FIMM-EMBL Group Leader, firstname.lastname@example.org