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Bioinformatics Advance Access originally published online on January 15, 2009
Bioinformatics 2009 25(5):592-598; 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,{dagger}, Stefanie Hartmann 2,5,{dagger}, Mayetri Gupta 3,*, Joseph G. Ibrahim 4 and Todd J. Vision 5

1Department of Mathematics, Illinois State University, Normal, IL, USA, 2Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany, 3Department of Biostatistics, Boston University, Boston, MA, 4Department of Biostatistics and 5Department of Biology, University of North Carolina at Chapel Hill, USA

*To whom correspondence should be addressed.


  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), which are partial sequences of expressed genes, 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 code for fitting these models are available from: http://people.bu.edu/gupta/software.htm.

Contact: gupta{at}bu.edu

Supplementary information: Supplemantary data are available at Bioinformatics online.

{dagger}The author wish it to be known that, in their opinion, the first two authors should be regarded as joint First authors.

Associate Editor: Martin Bishop

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

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