RT Journal Article
SR Electronic
T1 ReproTox-KG: Toxicology Knowledge Graph for Structural Birth Defects
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.15.508198
DO 10.1101/2022.09.15.508198
A1 John Erol Evangelista
A1 Daniel J. B. Clarke
A1 Zhuorui Xie
A1 Giacomo B. Marino
A1 Vivian Utti
A1 Taha M. Ahooyi
A1 Sherry L. Jenkins
A1 Deanne Taylor
A1 Cristian G. Bologa
A1 Jeremy J. Yang
A1 Jessica L. Binder
A1 Praveen Kumar
A1 Christophe G. Lambert
A1 Jeffrey S. Grethe
A1 Eric Wenger
A1 Tudor I. Oprea
A1 Bernard de Bono
A1 Avi Ma’ayan
YR 2022
UL http://biorxiv.org/content/early/2022/09/17/2022.09.15.508198.abstract
AB 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.Competing Interest StatementTudor I. Oprea, Cristian G. Bologa, and Jessica Binder have been compensated for their work as employees of Roivant Sciences Inc. All other authors declare no conflicts of interest.