Tandy J. Warnow Department of Computer Science University of Arizona Tucson AZ USA email: tandy cs, arizona, edu Abstract In an earlier paper, we described a new method for phylogenetic tree reconstruction called the Disk Covering Method, or DCM. This is a general method which can be used with an)' existing phylogenetic method in order to improve its performance, lCre showed analytically and experimentally that when DCM is used in conjunction with polynomial time distance-based methods, it improves the accuracy of the trees reconstructed. In this paper, we discuss a variant on DCM, that we call DCM2. DCM2 is designed to be used with phylogenetic methods whose objective is the solution of NPhard optimization problems. We also motivate the need for solutions to NPhard optimization problems by showing that on some very large and important datasets, the most popular (and presumably best performing) polynomial time distance methods have poor accuracy. Introduction 118 HUSON The accurate recovery of the phylogenetic branching order from molecular sequence data is fundamental to many problems in biology. Multiple sequence alignment, gene function prediction, protein structure, and drug design all depend on phylogenetic inference. Although many methods exist for the inference of phylogenetic trees, biologists who specialize in systematics typically compute Maximum Parsimony (MP) or Maximum Likelihood (ML) trees because they are thought to be the best predictors of accurate branching order. Unfortunately, MP and ML optimization problems are NPhard, and typical heuristics use hill-climbing techniques to search through an exponentially large space. When large numbers of taxa are involved, the computational cost of MP and ML methods is so great that it may take years of computation for a local minimum to be obtained on a single dataset (Chase et al. 1993; Rice, Donoghue, & Olmstead 1997). It is because of this computational cost that many biologists resort to distance-based calculations, such as Neighbor-Joining (NJ) (Saitou & Nei 1987), even though these may poor accuracy when the diameter of the tree is large (Huson et al. 1998). As DNA sequencing methods advance, large, divergent, biological datasets are becoming commonplace. For example, the February, 1999 issue of Molecular Biology and Evolution contained five distinct datascts of more than 50 taxa, and two others that had been pruned below that.
Jan-11-2006, 15:59:44 GMT