Bioinformatics Advance Access published online on November 16, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl577
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1 State Key Lab for Turbulence and Complex Systems and Center for Theoretical Biology, Peking University, Beijing 100871, China
* To whom correspondence should be addressed.
Motivation: Heterochronous gene sequence data is important for characterizing the evolutionary processes of fast-evolving organisms such as RNA viruses. A limited set of algorithms exists for estimating the rate of nucleotide substitution and inferring phylogenetic trees from such data. The authors here present a new method, Tree and Rate Estimation by Local Evaluation (TREBLE), that robustly calculates the rate of nucleotide substitution and phylogeny with several orders of magnitude improvement in computational time. Methods: For the basis of its rate estimation TREBLE novelly utilizes a geometric interpretation of the molecular clock assumption to deduce a local estimate of the rate of nucleotide substitution for triplets of dated sequences. Averaging the triplet estimates via a variance weighting yields a global estimate of the rate. From this value, an iterative refinement procedure relying on statistical properties of the triplets then generates a final estimate of the global rate of nucleotide substitution. The estimated global rate is then utilized to find the tree from the pairwise distance matrix via an UPGMA-like algorithm. Results: Simulation studies show that TREBLE estimates the rate of nucleotide substitution with point estimates comparable with the best of available methods. Confidence intervals are comparable with that of BEAST. TREBLE's phylogenetic reconstruction is significantly improved over the other distance matrix method but not as accurate as the Bayesian algorithm. Compared with three other algorithms, TREBLE reduces computational time by a minimum factor of 3000. Relative to the algorithm with the most accurate estimates for the rate of nucleotide substitution (i.e. BEAST), TREBLE is over 10,000 times more computationally efficient. Availability: jdobrien.bol.ucla.edu/TREBLE.html. Associate Editor: Joaquin Dopazo *These authors contributed equally to this work.
Received April 1, 2006
Revised November 8, 2006
Accepted November 10, 2006
Article
Tree and rate estimation by local evaluation of heterochronous nucleotide data
Zhu Yang 1 *, John D. O'Brien 2 *, Xiaobin Zheng 1, Huai-Qiu Zhu 1, and Zhen-Su She 3 *
2 Department of Biomathematics, University of California, Los Angeles, Los Angeles, CA 90095, USA
3 State Key Lab for Turbulence and Complex Systems and Center for Theoretical Biology, Peking University, Beijing 100871, China; Department of Mathematics, University of California, Los Angeles, Los Angeles, CA 90095, USA
Zhen-Su She, E-mail: she{at}math.ucla.edu
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