Illuminating the Druggable Genome

Out of the nearly 20,000 protein-coding genes in the human genome, approximately 3,000 are estimated to be part of the druggable genome, the subset of genes expressing proteins with the ability to bind drug-like molecules. Yet, less than ten percent of the druggable proteins are currently targeted by FDA-approved drugs. A significant number of those remaining are understudied and will be the focus of the Implementation Phase of the IDG. 

The IDG program was funded as a three-year pilot starting in 2014 with two goals. The first goal was to integrate information about understudied druggable proteins from disparate sources into a single informatics site. The second goal was to foster technology development to enable the determination of function and therapeutic potential of understudied druggable proteins at sufficient scale. The program is on track to be successful in accomplishing both of these goals.

The Implementation Phase of the IDG Program will capitalize on the information gathered and the technologies developed in the first three years to elucidate the function of the unstudied proteins of the druggable genome.

Specifically, the Implementation Phase of the program is intended to:

1. Expand the informatics tools developed in the Pilot Phase to include additional data and allow users to access a wide range of information on sets of proteins. This goal will be supported by the Knowledge Management Center (KMC.) The KMC identifies and scientifically justifies the data and resources it gathers, enabling the biomedical community to easily identify and prioritize protein targets within any gene family for further study. The KMC will be managed by Dr. Tudor Oprea from the University of New Mexico Health Science Center and Drs. Avi Ma'ayan and Joel Dudley from the Icahn School of Medicine at Mount Sinai.
2. Elucidate the function of understudied proteins from three key druggable protein families: non-olfactory G-protein coupled receptors (GPCRs), ion channels, and protein kinases. This goal will be supported by three Data and Resource Generation Centers (DRGCs.) The objectives are to establish a set of integrated technology platforms and generate novel data and tools revealing the molecular, cellular, and/or physiological role of understudied proteins in these three families. Dr. Bryan Roth, Dr. Brian Shoichet, and Dr. Gary Johnson at the University of North Carolina at Chapel Hill have been awarded grants to fund DRGCs that study GPCRs and kinases. Dr. Lily Jan and Dr. Michael McManus from the University of California at San Francisco have been awarded a grant that supports a DRGC to study ion channels.
3. Disseminate the IDG-related resources and data to the great scientific community. This goal will be supported by the Resource Dissemination and Outreach Center (RDOC.) The overall goals of the RDOC are to ensure facile access to resources, including reagents, for the research community and to facilitate collaboration and communication among IDG Consortium participants. The RDOC will be managed by Dr. Stephan Schürer from the University of Miami School of Medicine and Drs. Larry Sklar and Tudor Oprea from the University of New Mexico Health Science Center.
4. Build a set of Cutting Edge Informatics Tools (CEITs) that will augment the capability of the KMC as well as the broader IDG Consortium in the following ways: (1) by developing and deploying tools to enhance the community's ability to process, analyze, and visualize IDG data, (2) to prioritize new data resources and methods to be incorporated into Pharos that will strengthen predictions about physiological and disease associations around the understudied proteins, and (3) by developing methods to prioritize understudied IDG families (non-olfactory GPCRs, protein kinases, and ion channels) for deeper study using experimental assays both within the IDG pipeline or by the larger community. The CEITs will be developed by Drs. Natarajan Kannan and Krysztof Kochut from the University of Georgia, Drs Nicholas Robinson and Christopher Mungall from Jackson Laboratories, Drs. Guanming Wu, Peter Deustachio and Lincoln Stein from the Oregon Health and Science University, and Dr. Tudor Oprea from New Mexico University.

By focusing on understudied genes similar to those for which there are already many drugs, the IDG hopes to find potential targets for medications to treat and cure some of our most burdensome diseases - and then share what was learned so that all can build on this knowledge.