Bayesian Integrated Testing Strategy (ITS) for Skin Sensitization Potency Assessment: a Decision Support System for Quantitative Weight of Evidence and Adaptive Testing Strategy
Presented at the 5th Annual BayesiaLab Conference in Paris, September 25–October 4, 2017.
Dr. Joanna S. Jaworska
Principal Scientist, Modeling and Simulation, Biological Systems, Brussels Innovation Center, Procter & Gamble
Abstract
The presented Bayesian network Integrated Testing Strategy (ITS-3) for skin sensitization potency assessment is a decision support system for a risk assessor that provides the quantitative weight of evidence, leading to a mechanistically interpretable potency hypothesis, and formulates an adaptive testing strategy for a chemical. The system was constructed with an aim to improving precision and accuracy for predicting LLNA potency beyond ITS-2 (Jaworska et al., J Appl Toxicol 33(11):1353–1364, 2013) by improving the representation of chemistry and biology. Among novel elements are corrections for bioavailability both in vivo and in vitro as well as consideration of the individual assays’ applicability domains in the prediction process. In the ITS-3 structure, three validated alternative assays, DPRA, KeratinoSens, and h-CLAT, represent the first three key events of the adverse outcome pathway for skin sensitization. The skin sensitization potency prediction is provided as a probability distribution over four potency classes. The probability distribution is converted to Bayes factors to 1) remove prediction bias introduced by the training set potency distribution and 2) express uncertainty in a quantitative manner, allowing transparent and consistent criteria to accept a prediction.