Integration of the Drug-Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts

Abstract

The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from publications, databases, and other web-based sources. Drug, gene, and interaction data are normalized and merged into conceptual groups. The information contained in this resource is available to users through a straightforward search interface, an application programming interface (API), and TSV data downloads. DGIdb 4.0 is the latest major version release of this database. A primary focus of this update was integration with crowdsourced efforts, leveraging the Drug Target Commons for community-contributed interaction data, Wikidata to facilitate term normalization, and export to NDEx for drug-gene interaction network representations. Seven new sources have been added since the last major version release, bringing the total number of sources included to 41. Of the previously aggregated sources, 15 have been updated. DGIdb 4.0 also includes improvements to the process of drug normalization and grouping of imported sources. Other notable updates include the introduction of a more sophisticated Query Score for interaction search results, an updated Interaction Score, the inclusion of interaction directionality, and several additional improvements to search features, data releases, licensing documentation and the application framework.

Figure 1.

Overview of main components of DGIdb. Data sources are imported from outside resources (over 40 as of DGIdb 4.0), normalized and grouped with internal processes to prepare records to be displayed in DGIdb, and exported to TSV for download and integration with other resources. Process management is handled by Sidekiq for automation of importing, normalization and grouping, and exporting. A subset of new data sources are highlighted in green, a subset of updated pre-existing data sources are highlighted in blue. The updated sources highlighted in this figure are some of the sources that have been updated through manual curation. Information on additional sources and their status in DGIdb 4.0 can be found in Figure 2 and Supplementary Table S1. New features and technologies from DGIdb 4.0 are indicated with green dots, pre-existing features and technologies that have been updated are indicated with blue dots. The drug-gene network graph shown in the bottom right is an example of the data visualizations available on NDEx. Abbreviations: CMI = Caris Molecular Intelligence, FO = Foundation One, DTC = Drug Target Commons and HPA = Human Protein Atlas.

Figure 2.

DGIdb 4.0 content by source. The number of drug-gene interaction claims (first panel) and druggable gene categories (second panel) are separated into three categories: sources that are new, sources that existed in the DGIdb previously but have been updated for 4.0, or sources that existed previously but have not been updated. Abbreviations: CF = Clearity Foundation, CGI = Cancer Genome Interpreter, CMI = Caris Molecular Intelligence, DTC = Drug Target Commons, FO = Foundation One, GO = Gene Ontology, GTP = Guide to Pharmacology, HPA = Human Protein Atlas, IDG = Illuminating the Druggable Genome, JAX-CKB = JAX-Clinical Knowledgebase, MCG = My Cancer Genome, MSK = Memorial Sloan Kettering, OncoKB = Precision Oncology Knowledge Base, TALC = Targeted Agents in Lung Cancer, TDG = The Druggable Genome, TEND = Trends in the Exploration of Novel Drug targets and TTD = Therapeutic Target Database.

Figure 3.

Overview of DGIdb's new Query scores and Interaction scores. (A) Schematic of how each of the new scores is calculated within DGIdb. Gene and drug queries both return a Query Score that is dependent on the search terms. Each interaction has an Interaction Score that is calculated independently of other search terms. (B) Example of a Query Score changing based on the terms searched. In the first panel, only MEK1 and MEK2 were searched and the Query Score for the interaction between MEK1 and Cobimetinib was 8.09. In the second panel, BRAF and KRAS were added to the search query. These both interact with Cobimetinib and thus raise the Query Score to 16.18. (C) Example of Interaction Score. The panel on the left shows the interaction between ZEB1 and Salinomycin. This is the only interaction for Salinomycin and thus it has a high Interaction Score. The panel on the right shows the interaction between ZEB1 and Doxorubicin. Doxorubicin is involved in 103 interactions within DGIdb and thus has a much lower Interaction Score. Note that over time, as sources are updated and new claims are added, both Query Scores and Interaction Scores may change.