Relationship between prediction accuracy and uncertainty in compound potency prediction using deep neural networks and control models

The assessment of prediction variance or uncertainty contributes to the evaluation of machine learning models. In molecular machine learning, uncertainty quantification is an evolving area of research where currently no standard approaches or general guidelines are available. We have carried out a detailed analysis of deep neural network variants and simple control models for compound potency prediction to study relationships between prediction accuracy and uncertainty. For comparably accurate predictions obtained with models of different complexity, highly variable prediction uncertainties were detected using different metrics. Furthermore, a strong dependence of prediction characteristics and uncertainties on potency levels of test compounds was observed, often leading to over- or under-confident model decisions with respect to the expected variance of predictions. Moreover, neural network models responded very differently to training set modifications. Taken together, our findings indicate that there is only little, if any correlation between compound potency prediction accuracy and uncertainty, especially for deep neural network models, when predictions are assessed on the basis of currently used metrics for uncertainty quantification.