DGIdb 2.0: mining clinically relevant drug-gene interactions

Abstract

The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that consolidates disparate data sources describing drug-gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specifically, nine new sources of drug-gene interactions have been added, including seven resources specifically focused on interactions linked to clinical trials. These additions have more than doubled the overall count of drug-gene interactions. The total number of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Finally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search functionality. With these updates, DGIdb represents a comprehensive and user friendly tool for mining the druggable genome for precision medicine hypothesis generation.

Figure 1.

DGIdb 1.0 and 2.0 content by source. Here, the number of genes with interactions (first panel), drug claims (second panel), drug–gene interaction claims (third panel), and druggable gene categories (fourth panel) are contrasted between DGIdb 1.0 and 2.0. In total, there are currently 2,644 (33 new to DGIdb 2.0) genes with interactions, 11,215 (1,023 new) drug claims, 40,017 (21,624 new) drug–gene interaction claims, and 18,500 (4,224 new) gene category claims. Abbreviations: CF = Clearity Foundation, GTP = Guide To Pharmacology, MCG = My Cancer Genome, TALC = Targeted Agents in Lung Cancer, TTD = Therapeutic Target Database, TEND = Trends in the Exploration of Novel Drug targets, and GO = Gene Ontology MSKCC = Memorial Sloan Kettering Cancer Center.

Figure 2.

DGIdb analysis of TCGA pan cancer recurrently mutated genes. (A) The 62 genes recurrently mutated in at least 5% of pan-cancer tumors, and the corresponding mutations observed in each tumor. (B) The number of potentially druggable genes among the 488 genes recurrently mutated in at least 2.5% of tumors, grouped by druggable gene categories. Colored bars indicate the fraction of each such category with interactions in a clinical evidence source, a non-clinical evidence source, or without interactions. GPCR = G-Protein Coupled Receptor, PI-3K = Phosphatidylinositol 3 Kinase, ST Kinase = Serine Threonine Kinase.

Figure 3.

The drug search interface. (A) Switching between gene and drug searches is as simple as selecting the mode with this button. (B) A search field that accepts a variety of drug or gene identifiers, and provides autocompletion suggestions for terms in the database. (C) Filters allow search results to be limited by the source database, curation level, and interaction type. (D) Users may select to review the results summary or more detailed views. (E) The results summary links genes and drugs by interaction and shows which of the queried resources contain interaction data. (F) The unique sources and PMIDs associated with each interaction are displayed to the user. These are combined to provide a score value that may be used for ranking the interactions.