Application of IATA – A case study in evaluating the global and local performance of a Bayesian network model for skin sensitization

<p>The information characterizing key events in an Adverse Outcome Pathway (AOP) can be generated from <i>in silico</i>, <i>in chemico</i>, <i>in vitro</i> and <i>in vivo</i> approaches. Integration of this information and interpretation for decision making are known as integrated approaches to testing and assessment (IATA). One such IATA was published by Jaworska et al., which describes a Bayesian network model known as ITS-2. The current work evaluated the performance of ITS-2 using a stratified cross-validation approach. We also characterized the impact of replacing the most significant component of the network, output from the expert system TIMES-SS, with structural alert information from the OECD Toolbox and Toxtree. Lack of structural alerts or TIMES-SS predictions yielded a sensitization potential prediction of 79%. If the TIMES-SS prediction was replaced by a structural alert indicator, the network predictivity increased up to 87%. The original network’s predictivity was 89%. The local applicability domain of the original ITS-2 network was also evaluated using reaction mechanistic domains to understand what types of chemicals ITS-2 was able to make the best predictions for. We found that the original network was successful at predicting which chemicals would be sensitizers, but not at predicting their potency.