Illuminating the Druggable Genome Data Coordinating Center - Engagement Plan with the CFDE

The Illuminating the Druggable Genome (IDG) consortium has two major goals: First, consolidate disparate protein- and disease-centric data types from multiple sources, integrate and harmonize them, then make them readily available to the public; Second, adapt and scale existing technologies to unveil the function of selected understudied members of the G-protein coupled receptor, ion channel and protein kinase families. Within the IDG, the Knowledge Management Center (IDG-KMC) integrates data from a wide range of chemical, biological and clinical resources, and has developed platforms that can be used to navigate understudied proteins (the “dark genome”), and their potential contribution to specific pathologies. Specifically, the IDG KMC is creating automated workflows to capture relevant public data for the entire proteome including manual annotations for the IDG list, covering five major areas: genotype, phenotype, expression, structure & function, and interactions & pathways. The IDG KMC designs, develops, implements, and updates the Target Central Repository Database (TCRD), a protein knowledgebase. The IDG KMC also expands, improves, and maintains Pharos, the TCRD portal, with support for automated data summaries, and active community feedback. Both TCRD and Pharos already integrate data from three Common Fund projects: GTEx, IMPC/KOMP and LINCS. The IDG KMC consolidates all the data generated by the Data and Resource Generation Centers (DRGCs), improving these data findability, accessibility, interoperability, reusability (FAIRness) and serving these data on the Pharos portal. The IDG program interface with the CFDE will enable hypothesis generation about novel drug targets for complex diseases. Many other Common Fund (CF) programs produce data about genetic variants and differentially expressed genes and proteins in the context of many complex human diseases. These genes in many cases do not have much information about them. For example, the CF program Undiagnosed Disease Network (UDN) identifies mutations in genes associated with undiagnosed diseases. The IDG-KMC has information from empirical evidence and from computational predictions about the function of these genes, which are commonly under-studied. Hence, data from the IDG-KMC can enrich the CFDE users who examine datasets that list genes and proteins. Several IDG resources provide gene landing pages that provide unique information about genes. These landing pages can be improved regarding FAIRness and can become a resource for the CFDE. In addition, data collected by the DRGCs and by the R03 IDG awardees can enrich the content of the CFDE portal. In particular, results from the R03 projects (Fig. 1) are currently not evaluated or stored in one place and are at risk of becoming lost. The CFDE engagement will ensure that data from this investment remains available long term.