Bio: Professor Shi Wei, from Nanjing University in China, is also the Vice Dean of the School of Environment. She has been engaged in the identification of toxic pollutants, especially developing many computational models and high-throughput toxicity testing methods for endocrine disruptors. She has published over 80 papers in the environmental journals including Environmental Science & Technology. One set of model from her group is available for download on VEGA HUB.

Abstract: A growing number of environmental contaminants have been proved to have reproductive toxicity to males and females. However, the unclear toxicological mechanism of reproductive toxicants limits the development of virtual screening methods. By consolidating androgen (AR)-/estrogen receptors (ERs)-mediated adverse outcome pathways (AOPs) with more than 8000 chemical substances, we uncovered relationships between chemical features, a series of pathway-related effects, and reproductive apical outcomes--changes in sex organ weights.

An AOP-based computational model named RepTox was developed and evaluated to predict and characterize chemicals’ reproductive toxicity for males and females (Figure 1). Results showed that RepTox has three outstanding advantages. I. Compared with the traditional models (37% and 81% accuracy, respectively), AOP significantly improved the predictive robustness of RepTox (96.3% accuracy). II. Compared with the application domain (AD) of models based on small in vivo datasets, AOP expanded the ADs of RepTox by 1.65-fold for male and 3.77-fold for female, respectively. III. RepTox implied that hydrophobicity, cyclopentanol substructure, and several topological indices (e.g., hydrogen-bond acceptors) were important, unbiased features associated with reproductive toxicants. Finally, RepTox was applied to the inventory of existing chemical substances of China and identified 2100 and 7281 potential toxicants to the male and female reproductive systems, respectively.