Hybrid Tree Reconstruction Methods Daniel Huson Scott Nettles Kenneth Rice Tandy Warnow Shibu Yooseph A major computational problem in Biology is the reconstruction of evolutionary trees for species sets, and accuracy is measured by comparing the {\em topology} of the reconstructed tree and the model tree. One of the major debates in the field is whether large evolutionary trees can be even approximately accurately reconstructed from biomolecular sequences of realistically bounded lengths (up to about 2000 nucleotides) using standard techniques (polynomial time methods and heuristics for NP-hard optimization problems). Using both analytical and experimental techniques, we show that on large trees, the two most popular methods in systematic biology, neighbor-joining and maximum parsimony heuristics, as well as two promising methods introduced by theoretical computer scientists, are all likely to have significant errors in the topology reconstruction of the model tree. In particular, we observe that the maximum evolutionary distance in the tree strongly negatively affects the accuracy of polynomial time distance methods (including neighbor-joining), an observation which has not yet appeared in the systematic biology literature. Our experimental results also suggest that the major tree reconstruction methods produce {\em different types} of topological errors, suggesting that a {\em combination} of these methods may have better performance than the major techniques themselves. We use these observations to propose a new general technique that combines the output of existing methods, thus producing {\em hybrid methods}. We study one such hybrid experimentally, and show that in significant parts of the parameter space, it achieves results that are equal to or better than the best of its components. Our experimental performance study examined more than a thousand sets of sequences simulated on more than a hundred different model trees. Presented at: WAE'98. 1998.