Aljarf Raghad, Tang Simon, Pires Douglas E V, Ascher David B
Structural Biology and Bioinformatics, Department of Biochemistry, University of Melbourne, Parkville 3052, Victoria, Australia.
Systems and Computational Biology, Bio21 Institute, University of Melbourne, Parkville 3052, Victoria, Australia.
J Chem Inf Model. 2023 Jan 23;63(2):432-441. doi: 10.1021/acs.jcim.2c00824. Epub 2023 Jan 3.
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 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/.
致畸药物可导致严重的胎儿畸形，从而对胎儿健康产生重大影响，但大多数已获批药物的致畸风险尚不清楚。在此，我们提出了一种新型预测工具embryoTox，它利用小分子化学结构的基于图的特征表示来预测和分类在孕期可能安全的分子。embryoTox使用了700多种具有特征性致畸效应的小分子的生物活性数据进行训练和验证。我们的最终模型在10倍交叉验证中达到了受试者操作特征曲线下面积（AUC）高达0.96，在非冗余盲测中达到了0.82，优于其他方法。我们相信，我们的预测工具将为优化筛选文库提供实用资源，以确定孕期使用的有效且安全的分子。为了提供一个简单且集成的平台来快速筛选潜在的安全分子及其风险因素，我们将embryoTox免费在线提供，网址为https://biosig.lab.uq.edu.au/embryotox/ 。
