Differences in learning characteristics between support vector machine and random forest models for compound classification revealed by Shapley value analysis.

The random forest (RF) and support vector machine (SVM) methods are mainstays in molecular machine learning (ML) and compound property prediction. We have explored in detail how binary classification models derived using these algorithms arrive at their predictions. To these ends, approaches from explainable artificial intelligence (XAI) are applicable such as the Shapley value concept originating from game theory that we adapted and further extended for our analysis. In large-scale activity-based compound classification using models derived from training sets of increasing size, RF and SVM with the Tanimoto kernel produced very similar predictions that could hardly be distinguished. However, Shapley value analysis revealed that their learning characteristics systematically differed and that chemically intuitive explanations of accurate RF and SVM predictions had different origins.