QSAR Modeling of Tox21 Challenge Stress Response and Nuclear Receptor Signaling Toxicity Assays

The ability to determine which environmental chemicals pose the greatest potential threats to human health remains one of the major concerns in regulatory toxicology. Computational methods that can accurately predict a chemical's toxic potential in silico are increasingly sought-after to replace in vitro high-throughput screening (HTS) as well as controversial and costly in vivo animal studies. To this end, we have built Quantitative Structure-Activity Relationship (QSAR) models of 12 stress response and nuclear receptor signaling pathways toxicity assays as part of the 2014 Tox21 Challenge. Our models were built using the Random Forest, Deep Neural Networks and various combinations of descriptors and balancing protocols. All of our models were statistically significant for each of the 12 assays with the balanced accuracy in the range between 0.58 and 0.82. Our results also show that models built with Deep Neural Networks had higher accuracy than those developed with simple machine learning algorithms and that dataset balancing led to a significant accuracy decrease.