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.

Association Between Hypoxia-Inducible Factor-2α (HIF-2α) Expression and Colorectal Cancer and Its Prognostic Role: a Systematic Analysis

“…HIF-2α expression was associated with a different survival benefit among some cancers (B-cell lymphoma and lung adenocarcinoma: OS, multiple myeloma: DSS, breast cancer: distant metastasis-free survival, liposarcoma: distant recurrence-free survival) (all HRs < 1, Ps < 0.05), indicating that HIF-2α expression may be a novel prognostic marker and potential therapeutic target for different cancer patient stratification. Moreover, we did not find the relevant drug information for the HIF-2α gene from the Drug-Gene Interaction Database (DGIdb) [56,57]. Further prospective and well-designed (multicenter, randomized controlled) studies are essential to translate the use of these findings into the clinical applications.…”

Exome-capture RNA sequencing of decade-old breast cancers and matched decalcified bone metastases

“…The clinically actionable gene set was obtained using the Drug Gene Interaction Database (DGBIdB 2.0) (69). Considering that metastatic fold change distributions calculated from log2normCPM values for all genes were slightly different for each case, stringent case-specific fold change thresholds were used to transform continuous fold change values into discrete "expression alterations."…”

The DrugAge database of aging-related drugs

“…To analyse enriched processes in the targets of compounds in DrugAge, we used DGIdb (Wagner et al ., 2016) to obtain a list of human gene interacting partners for all drugs in DrugAge (Experimental Procedures in Supporting information). Of 418 DrugAge compounds/substances, 90 were found to have a DGIdb record, resulting in a total of 411 distinct genes.…”

“…This was carried out by obtaining the 1124 human orthologues of genes that extend lifespan in model organisms using the GenAge database (Tacutu et al ., 2013). Of the 1124 genes, 287 (25.5%) were known to interact with drugs in DGIdb (Wagner et al ., 2016). Of these, 65 (29.3%) overlap with DrugAge targets (Fig.…”