A structural EM algorithm for phylogenetic inference

Nir Friedman, Matan Ninio, Itsik Pe'er, Tal Pupko

Research output: Contribution to journalArticlepeer-review

Abstract

A central task in the study of molecular evolution is the reconstruction of a phylogenetic tree from sequences of current-day taxa. The most established approach to tree reconstruction is maximum likelihood (ML) analysis. Unfortunately, searching for the maximum likelihood phylogenetic tree is computationally prohibitive for large data sets. In this paper, we describe a new algorithm that uses Structural Expectation Maximization (EM) for learning maximum likelihood phylogenetic trees. This algorithm is similar to the standard EM method for edge-length estimation, except that during iterations of the Structural EM algorithm the topology is improved as well as the edge length. Our algorithm performs iterations of two steps. In the E-step, we use the current tree topology and edge lengths to compute expected sufficient statistics, which summarize the data. In the M-Step, we search for a topology that maximizes the likelihood with respect to these expected sufficient statistics. We show that searching for better topologies inside the M-step can be done efficiently, as opposed to standard methods for topology search. We prove that each iteration of this procedure increases the likelihood of the topology, and thus the procedure must converge. This convergence point, however, can be a suboptimal one. To escape from such "local optima," we further enhance our basic EM procedure by incorporating moves in the fiavor of simulated annealing. We evaluate these new algorithms on both synthetic and real sequence data and show that for protein sequences even our basic algorithm finds more plausible trees than existing methods for searching maximum likelihood phylogenies. Furthermore, our algorithms are dramatically faster than such methods, enabling, for the first time, phylogenetic analysis of large protein data sets in the maximum likelihood framework.

Original languageEnglish
Pages (from-to)331-353
Number of pages23
JournalJournal of Computational Biology
Volume9
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Evolutionary tree
  • Expectation maximization
  • Inference
  • Maximum likelihood
  • Phylogeny
  • Simulated annealing
  • Structural EM

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