To systematically evaluate the performance of our semi-supervised metric approach, we first performed traditional unsupervised machine learning and compared the performance of the two models. To maintain a concise discussion of our results, the Supporting Information contains a detailed analysis and comparison of our unsupervised vs. semi-supervised machine learning results. Figure shows our clustering results using unsupervised machine learning on the C3F6 dataset, and Figure shows a comparison between the unsupervised and semisupervised results using the CF dataset on two different targets. Table summarizes the substructures that induce bioactivity as predicted from our unsupervised learning calculations.