The overall goal of the Illuminating the Druggable Genome Knowledge Management Center (IDG KMC) is to evaluate and organize (via the Data Organizing Core, DOC), present and visualize (via the User Interface Portal, UIP) and rank (in cooperation with the IDG Consortium) all prospective disease-linked proteins, as potential druggable targets for four protein superfamilies: G-protein-coupled receptors (GPCRs), nuclear receptors (NRs), ion channels (IC) and kinases. By combining data extracted from multiple sources, coupled with algorithmic processing, prediction and human curation, the emerging knowledge will be associated with the appropriate proteins. The KMC will link disease, pathway, protein, gene, chemical, bioactivity, drug discovery and clinical information elements from databases, literature, patents and other documents in the DOC Target Central Resource Database. TCRD will serve as primary source for the IDG Query Platform, the UlP-developed system that will enable scientists to access, visualize and analyze IDG-specific data. Coordinating DOC and UIP activities, the Administrative Core, AC, will assist with human curation by organizing class-specific External Target Panels to categorize proteins into 4 classes (Tclin - clinical; Tchem - manipulated by chemicals; Tmacro - manipulated by macromolecules; and Tdark - the genomic dark matter). Tissue and cellular localization for both disease and protein will serve as central filtes for ranking.
The specific aims of the KMC are based on the demonstrated experience of the Oprea-Sklar team at the University of New Mexico (data capture, processing, mining and modeling), and the Simeonov-led team at NCATS (software development, visualization and modeling), supported by teams based in Denmark, Florida and UK. Using automated tools, we performed disease-protein associations for each protein superfamily, obtained preliminary stratification (e.g., Tclin 22%, Tdark 30%), and designed Specific Aims that enable us to further annotate this genome subset. It is expected that within 12 months, the TCRD-based IDG Querly Platform will be operational, which may dramatically improve the target prioritization process for the research community at large and the IDG Consortium, in exploring dark matter for GPCRs, NRs, ICs and kinases.
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