Bayesian Integrated Testing Strategy (ITS) for Skin Sensitization Potency Assessment: a Decision Support System for Quantitative Weight of Evidence and Adaptive Testing Strategy
Dr. Joanna S. Jaworska, Principal Scientist, Modeling and Simulation, Biological Systems, Brussels Innovation Center, Procter & Gamble
Recorded at the 5th Annual BayesiaLab Conference in Paris on September 28, 2017.
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 quantitative weight of evidence, leading to a mechanistically interpretable potency hypothesis, and formulates adaptive testing strategy for a chemical. The system was constructed with an aim to improve precision and accuracy for predicting LLNA potency beyond ITS-2 (Jaworska et al., J Appl Toxicol 33(11):1353–1364, 2013) by improving 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 theprediction process. In ITS-3 structure, three validated alternative assays, DPRA, KeratinoSens and h-CLAT, represent 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.
Dr. Jaworska holds a M.S.E. in Water Engineering/ System analysis from Warsaw University of Technology, Poland, and Ph.D. in Computational Toxicology/ Mathematical Biology, University of Tennessee, Knoxville, USA, 1993. The focus of her graduate studies was simulation of biological systems dynamics and their interactions with chemicals. Today Dr. Jaworska hold position of Principal Scientist in Modeling and Simulation department and is responsible for Biological Systems. Dr. Jaworska has been working on computational methods to assess chemical effects and exposure to advance risk assessment methods applying dynamic system analysis, probabilistic reasoning, and uncertainty analysis and well as computational chemistry.