Overview of the Knowledge Management Center for Illuminating the Druggable Genome

Abstract

The Knowledge Management Center (KMC) for the Illuminating the Druggable Genome (IDG) project aims to aggregate, update, and articulate protein-centric data knowledge for the entire human proteome, with emphasis on the understudied proteins from the three IDG protein families. KMC collates and analyzes data from over 70 resources to compile the Target Central Resource Database (TCRD), which is the web-based informatics platform (Pharos). These data include experimental, computational, and text-mined information on protein structures, compound interactions, and disease and phenotype associations. Based on this knowledge, proteins are classified into different Target Development Levels (TDLs) for identification of understudied targets. Additional work by the KMC focuses on enriching target knowledge and producing DrugCentral and other data visualization tools for expanding investigation of understudied targets.

Keywords: database; druggable genome; knowledge management; pharos.

Figure 1.

Schematic showing data sources used to construct the Target Central Resource Database (TCRD). The data in TCRD are downloadable (http://juniper.health.unm.edu/tcrd/) and accessible via the Pharos website (https://pharos.nih.gov/).

Figure 2.

Title. (a) Overlap between drugs approved for humans and veterinary use. (b) Number of drugs in DrugCentral from 2017 to 2023.

Figure 3.

Data sources and the flow of information within the Target Importance and Novelty Explorer (TIN-X) informatics workflow. Users access the TIN-X user interface (UI) via a web browser. Unlike earlier versions of TIN-X, the UI and the REST application programming interface (API) are separate components. User activity on the TIN-X public web application results in API requests, which, in turn, access the TIN-X database. Users can query the data directly via the REST API, which is supported by Swagger documentation. The TIN-X UI, API, and database are all hosted in the cloud using Amazon Web Services. The TIN-X Database relies on the Target Central Resource Database (TCRD) for target data and the JensenLab DISEASES resource for text-mined PubMed content. Blue arrows depict the flow of data from these two major sources to the TIN-X database. Abbreviations: GPCR, G-protein-coupled receptor; ION, ion channels; OGPCR, orphan G-protein-coupled receptor; NR, nuclear receptor.

Figure 4.

Proteins that are associated with the disease of interest are analyzed on the Importance–Novelty plot generated from the Target Importance and Novelty Explorer (TIN-X) app within Pharos. Proteins that have more evidence of association with the disease are plotted in the upper part of the plot. Protein–disease associations of immediate interest are usually placed on the upper right area of the TIN-X plot and represent potential targets with high novelty. We have restricted our analysis to Tdark proteins (black markers).