Fast and accurate distance‐based phylogenetic placement using divide and conquer

Phylogenetic placement of query samples on an existing phylogeny is increasingly used in molecular ecology, including sample identification and microbiome environmental sampling. As the size of available reference trees used in these analyses continues to grow, there is a growing need for methods that place sequences on ultra-large trees with high accuracy. Distance-based placement methods have recently emerged as a path to provide such scalability while allowing flexibility to analyse both assembled and unassembled environmental samples. In this study, we introduce a distance-based phylogenetic placement method, APPLES-2, that is more accurate and scalable than existing distance-based methods and even some of the leading maximum-likelihood methods. This scalability is owed to a divide-and-conquer technique that limits distance calculation and phylogenetic placement to parts of the tree most relevant to each query. The increased scalability and accuracy enable us to study the effectiven...