Family-joining: A fast distance-based method for constructing generally labeled trees
Prabhav Kalaghatgi, Nico Pfeifer, Thomas Lengauer

The widely used model for evolutionary relationships is a bifurcating tree with all taxa/observations placed at the leaves. This is not appropriate for taxa that have been densely sampled across evolutionary time and may be in a direct ancestral relationship. In this paper, we present a fast distance-based agglomeration method called family-joining (FJ) for constructing so-called generally labeled trees in which taxa may be placed at internal vertices and the tree may contain polytomies. FJ constructs such trees on the basis of pairwise distances and a distance threshold. We tested two methods for threshold selection, FJ-BIC and FJ-CV, which minimize BIC and CV error, respectively. When compared with related methods on simulated data, FJ-BIC was among the best at reconstructing the correct tree across a wide range of simulation scenarios. FJ-BIC was applied to HIV sequences sampled from individuals involved in a known transmission chain. The FJ-BIC tree was found to be compatible with almost all transmission events. On average, internal branches in the FJ-BIC tree have higher bootstrap support than branches in the leaf-labeled bifurcating tree constructed using RAxML. 36% and 25% of the internal branches in the FJ-BIC tree and RAxML tree, respectively, have bootstrap support greater than 70%. To the best of our knowledge the method presented here is the first attempt at modeling the evolutionary relationships of densely sampled pathogens using generally labeled trees.