title: Tree and rate estimation by local evaluation of heterochronous nucleotide data.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  jdobrien.bol.ucla.edu/TREBLE.html
authors.affiliation: State Key Lab for Turbulence and Complex Systems and Center for Theoretical Biology, Peking University, Beijing 100871, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yang
authors.forename: John D
authors.initials: JD
authors.lastname: O'Brien
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zheng
authors.forename: Huai-Qiu
authors.initials: HQ
authors.lastname: Zhu
authors.forename: Zhen-Su
authors.initials: ZS
authors.lastname: She
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D004252:DNA Mutational Analysis / Q000379:methods*; D019143:Evolution, Molecular; D007700:Kinetics; D008957:Models, Genetic; D009711:Nucleotides / Q000235:genetics*; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*; D013997:Time Factors
chemical_list: D009711:Nucleotides