Supervised learning on phylogenetically distributed data

The ability to develop robust machine-learning (ML) models is considered imperative to the adoption of ML techniques in biology and medicine fields. This challenge is particularly acute when data available for training is not independent and identically distributed (iid), in which case trained models are vulnerable to out-of-distribution generalization problems. Of particular interest are problems where data correspond to observations made on phylogenetically related samples (e.g. We introduce DendroNet, a new approach to train neural networks in the context of evolutionary data. DendroNet explicitly accounts for the relatedness of the training/testing data, while allowing the model to evolve along the branches of the phylogenetic tree, hence accommodating potential changes in the rules that relate genotypes to phenotypes. Using simulated data, we demonstrate that DendroNet produces models that can be significantly better than non-phylogenetically aware approaches. DendroNet also outperforms other approaches at two biological tasks of significant practical importance: antiobiotic resistance prediction in bacteria and trophic level prediction in fungi. In supervised machine learning, most work operates under the assumption that the available data points are independent and identically distributed. Yet in many bioinformatics applications, this is not the case. This assumption is particularly strongly violated when examples are phylogenetically or genealogically related.