UPGMA (Unweighted Pair Group Method with Arithmetic Mean) is a widely used clustering method. Here we show that UPGMA is a greedy heuristic for the normalized equidistant minimum evolution (NEME) problem, that is, finding a rooted tree that minimizes the minimum evolution score relative to the dissimilarity matrix among all rooted trees with the same leaf-set in which all leaves have the same distance to the root. We prove that the NEME problem is NP-hard. In addition, we present some heuristic and approximation algorithms for solving the NEME problem, including a polynomial time algorithm that yields a binary, rooted tree whose NEME score is within O(log^2 n) of the optimum. We expect that these results to eventually provide further insights into the behavior of the UPGMA algorithm.
Due to its speed, the distance approach remains the best hope for building phylogenies on very large sets of taxa. Recently (R. Desper and O. Gascuel, J. Comp. Biol. 9:687-705, 2002), we introduced a new "balanced" minimum evolution (BME) principle, based on a branch length estimation scheme of Y. Pauplin (J. Mol. Evol. 51:41-47, 2000). Initial simulations suggested that FASTME, our program implementing the BME principle, was more accurate than or equivalent to all other distance methods we tested, with running time significantly faster than Neighbor-Joining (NJ). This article further explores the properties of the BME principle, and it explains and illustrates its impressive topological accuracy. We prove that the BME principle is a special case of the weighted least-squares approach, with biologically meaningful variances of the distance estimates. We show that the BME principle is statistically consistent. We demonstrate that FASTME only produces trees with positive branch lengths, a feature that separates this approach from NJ (and related methods) that may produce trees with branches with biologically meaningless negative lengths. Finally, we consider a large simulated data set, with 5,000 100-taxon trees generated by the Aldous beta-splitting distribution encompassing a range of distributions from Yule-Harding to uniform, and using a covarion-like model of sequence evolution. FASTME produces trees faster than NJ, and much faster than WEIGHBOR and the weighted least-squares implementation of PAUP*. Moreover, FASTME trees are consistently more accurate at all settings, ranging from Yule-Harding to uniform distributions, and all ranges of maximum pairwise divergence and departure from molecular clock. Interestingly, the covarion parameter has little effect on the tree quality for any of the algorithms. FASTME is freely available on the web. Distance-based phylogenetic methods attempt to reconstruct an accurate phylogenetic tree from an estimated matrix of pairwise distances between taxa. This paper examines two distance-based algorithms (GreedyBME and FastME) that are based on the principle of minimizing the balanced minimum evolution score of the output tree in relation to the given estimated distance matrix. This is also the principle that underlies the neighbor-joining (NJ) algorithm. We show that GreedyBME and FastME both reconstruct the entire correct tree if the input data are quartet consistent, and also that if the maximum error of any distance estimate is @math , then both algorithms output trees containing all sufficiently long edges of the true tree: those having length at least @math . That is to say, the algorithms have edge safety radius 1 3. In contrast, quartet consistency of the data is not sufficient to guarantee the NJ algorithm reconstructs the correct tree, and moreover, the NJ algorithm has edge safety radius of 1 4: Only edges of the true tree of length at least @math can be guaranteed to appear in the output. These results give further theoretical support to the experimental evidence suggesting FastME is a more suitable distance-based phylogeny reconstruction method than the NJ algorithm. UPGMA is a heuristic method identifying the least squares equidistant phylogenetic tree given empirical distance data among @math taxa. We study this classic algorithm using the geometry of the space of all equidistant trees with @math leaves, also known as the Bergman complex of the graphical matroid for the complete graph @math . We show that UPGMA performs an orthogonal projection of the data onto a maximal cell of the Bergman complex. We also show that the equidistant tree with the least (Euclidean) distance from the data is obtained from such an orthogonal projection, but not necessarily given by UPGMA. Using this geometric information we give an extension of the UPGMA algorithm. We also present a branch and bound method for finding the best equidistant tree. Finally, we prove that there are distance data among @math taxa which project to at least @math equidistant trees. Many phylogenetic algorithms search the space of possible trees using topological rearrangements and some optimality criterion. FastME is such an approach that uses the balanced minimum evolution (BME) principle, which computer studies have demonstrated to have high accuracy. FastME includes two variants: balanced subtree prune and regraft (BSPR) and balanced nearest neighbor interchange (BNNI) . These algorithms take as input a distance matrix and a putative phylogenetic tree. The tree is modified using SPR or NNI operations, respectively, to reduce the BME length relative to the distance matrix, until a tree with (locally) shortest BME length is found. Following computer simulations, it has been conjectured that BSPR and BNNI are consistent, i.e. for an input distance that is a tree-metric, they converge to the corresponding tree. We prove that the BSPR algorithm is consistent. Moreover, even if the input contains small errors relative to a tree-metric, we show that the BSPR algorithm still returns the corresponding tree. Whether BNNI is consistent remains open. Several popular methods for phylogenetic inference (or hierarchical clustering) are based on a matrix of pairwise distances between taxa (or any kind of objects): The objective is to construct a tree with branch lengths so that the distances between the leaves in that tree are as close as possible to the input distances. If we hold the structure (topology) of the tree fixed, in some relevant cases (e.g., ordinary least squares) the optimal values for the branch lengths can be expressed using simple combinatorial formulae. Here we define a general form for these formulae and show that they all have two desirable properties: First, the common tree reconstruction approaches (least squares, minimum evolution), when used in combination with these formulae, are guaranteed to infer the correct tree when given enough data (consistency); second, the branch lengths of all the simple (nearest neighbor interchange) rearrangements of a tree can be calculated, optimally, in quadratic time in the size of the tree, thus allowing the efficient application of hill climbing heuristics. The study presented here is a continuation of that by Mihaescu and Pachter on branch length estimation [Mihaescu R, Pachter L (2008) Proc Natl Acad Sci USA 105:13206–13211]. The focus here is on the inference of the tree itself and on providing a basis for novel algorithms to reconstruct trees from distances. Distance-based methods such as UPGMA (Unweighted Pair Group Method with Arithmetic Mean) continue to play a significant role in phylogenetic research. We use polyhedral combinatorics to analyze the natural subdivision of the positive orthant induced by classifying the input vectors according to tree topologies returned by the algorithm. The partition lattice informs the study of UPGMA trees. We give a closed form for the extreme rays of UPGMA cones on n taxa, and compute the spherical volumes of the UPGMA cones for small n.