Deep ensemble learning over the microbial phylogenetic tree (DeepEn-Phy).

Successful prediction of clinical outcomes facilitates tailored diagnosis and treatment. The microbiome has been shown to be an important biomarker to predict host clinical outcomes. Further, the incorporation of microbial phylogeny, the evolutionary relationship among microbes, has been demonstrated to improve prediction accuracy. We propose a phylogeny-driven deep neural network (PhyNN) and develop an ensemble method, DeepEn-Phy, for host clinical outcome prediction. The method is designed to optimally extract features from phylogeny, thereby take full advantage of the information in phylogeny while harnessing the core principles of phylogeny (in contrast to taxonomy). We apply DeepEn-Phy to a real large microbiome data set to predict both categorical and continuous clinical outcomes. DeepEn-Phy demonstrates superior prediction performance to existing machine learning and deep learning approaches. Overall, DeepEn-Phy provides a new strategy for designing deep neural network architectures within the context of phylogeny-constrained microbiome data.