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Heads or tails: a simple reliability check for multiple sequence alignments.

Giddy Landan1, Dan Graur

  • 1Department of Biology & Biochemistry, University of Houston, TX, USA. giddy.landan@gmail.com

Molecular Biology and Evolution
|March 28, 2007
PubMed
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We introduce a practical method to assess multiple sequence alignment quality by comparing alignments of forward and reversed sequences. This heads-or-tails (HoT) approach quantifies alignment uncertainty and its impact on downstream analyses like phylogenetics.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Assessing multiple sequence alignment (MSA) quality is crucial but lacks practical methods.
  • Existing alignment tools often do not provide reliable quality metrics for real-world applications.

Purpose of the Study:

  • To develop a simple, practical methodology for identifying and quantifying uncertainties in MSAs.
  • To evaluate the impact of alignment uncertainties on subsequent bioinformatics analyses.

Main Methods:

  • The heads-or-tails (HoT) methodology was developed, comparing alignments of original sequences with alignments of reversed sequences.
  • The degree of agreement between 'heads' and 'tails' alignments quantifies reliability.
  • Alignment-dependent analyses were performed separately on both sets of alignments to assess robustness.

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Main Results:

  • The HoT methodology effectively identifies and quantifies MSA uncertainties.
  • Phylogenetic reconstruction using Neighbor-Joining methods showed less sensitivity to alignment errors compared to maximum likelihood and Bayesian methods.
  • Analysis of the BaliBASE dataset and a Drosophila melanogaster chemoreceptor superfamily dataset demonstrated HoT's utility.

Conclusions:

  • The HoT methodology provides a practical approach to assess MSA quality and analytical robustness.
  • Alignment uncertainties can significantly impact phylogenetic reconstruction, with Neighbor-Joining being more robust to these errors.