Fig. 1. Heterogeneity through Discriminative Analysis (HYDRA) algorithm and subtype selection.

A HYDRA is a semi-supervised machine learning algorithm that reveals homogenous subtypes within a clinical group by maximizing subtype-specific margins between patient subtypes and controls, while adjusting for covariates. B The stability of the clustering solution after cross-validation was evaluated over a resolution range of 2–10 clusters (2–6 shown here), and was quantified by the adjusted rand index (ARI). The maximum ARI was seen with three subtypes.