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Bioinformatics Advance Access published online on January 15, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp015
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A hierarchical model for incomplete alignments in phylogenetic inference

Fuxia Cheng 1,*, Stefanie Hartmann 2,5,*, Mayetri Gupta 3,{dagger}, Joseph G Ibrahim 4 and Todd J. Vision 5

1Department of Mathematics, Illinois State University, U.S.A.
2Institute for Biochemistry and Biology, University of Potsdam, Germany
3Department of Biostatistics, Boston University, U.S.A.
4Department of Biostatistics, University of North Carolina at Chapel Hill, U.S.A.
5Department of Biology, University of North Carolina at Chapel Hill, U.S.A.

{dagger}To whom correspondence should be addressed. Dr. Mayetri Gupta, E-mail: gupta{at}bu.edu


  Abstract

Motivation: Full-length DNA and protein sequences that span the entire length of a gene are ideally used for multiple sequence alignments (MSAs) and the subsequent inference of their relationships. Frequently, however, MSAs contain a substantial amount of missing data. For example, expressed sequence tags (ESTs) are the predominant source of sequence data for many organisms. The patterns of missing data typical for EST-derived alignments greatly compromise the accuracy of estimated phylogenies.

Results: We present a statistical method for inferring phylogenetic trees from EST-based incomplete MSA data. We propose a class of hierarchical models for modeling pairwise distances between the sequences, and develop a fully Bayesian approach for estimation of the model parameters. Once the distance matrix is estimated, the phylogenetic tree may be constructed by applying neighbor-joining (or any other algorithm of choice). We also show that maximizing the marginal likelihood from the Bayesian approach yields similar results to a profile likelihood estimation. The proposed methods are illustrated using simulated protein families, for which the true phylogeny is known, and one real protein family.

Availability: R codes for fitting these models are available from: http://people.bu.edu/gupta/software.htm.

Contact: gupta{at}bu.edu

Associate Editor: Prof. Martin Bishop

These authors contributed equally to this work

Received on September 25, 2008; revised on January 5, 2009; accepted on January 5, 2009

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