The 2021 update of the EPA's adverse outcome pathway database

Abstract

The EPA developed the Adverse Outcome Pathway Database (AOP-DB) to better characterize adverse outcomes of toxicological interest that are relevant to human health and the environment. Here we present the most recent version of the EPA Adverse Outcome Pathway Database (AOP-DB), version 2. AOP-DB v.2 introduces several substantial updates, which include automated data pulls from the AOP-Wiki 2.0, the integration of tissue-gene network data, and human AOP-gene data by population, semantic mapping and SPARQL endpoint creation, in addition to the presentation of the first publicly available AOP-DB web user interface. Potential users of the data may investigate specific molecular targets of an AOP, the relation of those gene/protein targets to other AOPs, cross-species, pathway, or disease-AOP relationships, or frequencies of AOP-related functional variants in particular populations, for example. Version updates described herein help inform new testable hypotheses about the etiology and mechanisms underlying adverse outcomes of environmental and toxicological concern.

Fig. 1

AOP-DB Data Structure. Green, Ovals indicate data tables in the AOP-DB SQL relational database; Blue, Diamonds indicate local, post-processing files necessary, where modified data are stored; Yellow, Rectangles indicate corresponding subroutines necessary to process source data; and Red, Diamonds indicate publicly available, third party source data included in AOP-DB v.2. Arrow edges indicate foreign key relationships.

Fig. 2

AOP Tissue Network Visualization Tool illustrates the tissue-gene network built with user query for SREBF1 for hepatocyte tissue. Associated AOPs for SREBF1 are listed in the left-hand pane.

Fig. 3

Minor allele frequency (MAF) distribution for SNPs associated with 104 functionally relevant Human AOP-genes for five 1000 Genomes Super populations: American (Blue); African (Yellow); East Asian (Red); European (Green); South Asian (Black).

Fig. 4

AOP-DB search page illustrating “Basic Search” task bar with accepted user input types and download file specificity.

Fig. 5

AOP-DB Semantic Mapping using the Resource Description Framework (RDF) illustrating Chemical-Gene Interaction, Protein-Protein Interaction, ToxCast Assay, and Pathway tables.