ReproTox-KG: Toxicology Knowledge Graph for Structural Birth Defects

Birth defects are functional and structural abnormalities that impact 1 in 33 births in the United States. Birth defects have been attributed to genetic as well as other factors, but for most birth defects there are no known causes. Small molecule drugs, cosmetics, foods, and environmental pollutants may cause birth defects when the mother is exposed to them during pregnancy. These molecules may interfere with the process of normal fetal development. To characterize associations between small molecule compounds and their potential to induce specific birth abnormalities, we gathered knowledge from multiple sources to construct a reproductive toxicity Knowledge Graph (ReproTox-KG) with an initial focus on associations between birth defects, drugs, and genes. Specifically, to construct ReproTox-KG we gathered data from drug/birth-defect associations from co-mentions in published abstracts, gene/birth-defect associations from genetic studies, drug- and preclinical-compound-induced gene expression data, known drug targets, genetic burden scores for all human genes, and placental crossing scores for all small molecules in ReproTox-KG. Using the data stored within ReproTox-KG, we scored 30,000 preclinical small molecules for their potential to induce birth defects. Querying the ReproTox-KG, we identified over 500 birth-defect/gene/drug cliques that can be used to explain molecular mechanisms for drug-induced birth defects. The ReproTox-KG is provided as curated tables and via a web-based user interface that can enable users to explore the associations between birth defects, approved and preclinical drugs, and human genes.