Illustration of PHACTboost, a tool leveraging a gradient-boosted decision-tree machine learning model to predict the effects of amino acid substitutions in diseases. The input features, derived from phylogenetic trees, establish the precise evolutionary history of proteins. This integration symbolizes the application of evolutionary insights in advanced computational techniques within modern bioinformatics (DOI: https://doi.org/10.1093/molbev/msae136). Artwork by Nehircan Özdemir.