posted on 2023-01-03, 17:39authored byRaghad Aljarf, Simon Tang, Douglas E. V. Pires, David B. Ascher
Teratogenic drugs can lead to extreme fetal malformation
and consequently
critically influence the fetus’s health, yet the teratogenic
risks associated with most approved drugs are unknown. Here, we propose
a novel predictive tool, embryoTox, which utilizes a graph-based signature
representation of the chemical structure of a small molecule to predict
and classify molecules likely to be safe during pregnancy. embryoTox
was trained and validated using in vitro bioactivity
data of over 700 small molecules with characterized teratogenicity
effects. Our final model achieved an area under the receiver operating
characteristic curve (AUC) of up to 0.96 on 10-fold cross-validation
and 0.82 on nonredundant blind tests, outperforming alternative approaches.
We believe that our predictive tool will provide a practical resource
for optimizing screening libraries to determine effective and safe
molecules to use during pregnancy. To provide a simple and integrated
platform to rapidly screen for potential safe molecules and their
risk factors, we made embryoTox freely available online at https://biosig.lab.uq.edu.au/embryotox/.