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Characterization of multiple sequence alignment errors using complete-likelihood score and position-shift map.

Kiyoshi Ezawa1,2

  • 1Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, 820-8502, Japan. kezawa.ezawa3@gmail.com.

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|March 20, 2016
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Summary
This summary is machine-generated.

New tools, the complete-likelihood score and position-shift map, help identify errors in multiple sequence alignments (MSAs). These methods reveal that current aligners often make errors, even when producing seemingly optimal results.

Keywords:
ErrorInsertion/deletion (indel)LikelihoodMSA space explorationMultiple sequence alignment (MSA)Power-lawProbability distributionStochastic evolutionary modelVisualization

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Area of Science:

  • Computational Biology
  • Bioinformatics
  • Evolutionary Biology

Background:

  • Multiple sequence alignment (MSA) is fundamental for homology-based sequence analysis.
  • Characterizing errors in state-of-the-art aligners is crucial for improving MSA accuracy.
  • This study introduces the complete-likelihood score and position-shift map to analyze MSA errors.

Purpose of the Study:

  • To develop and apply novel tools for characterizing errors in multiple sequence alignments (MSAs).
  • To evaluate the performance of leading MSA aligners (MAFFT and Prank) using these new analytical methods.
  • To understand the nature and extent of alignment errors in simulated datasets.

Main Methods:

  • Developed the complete-likelihood score to assess MSA quality based on evolutionary models.
  • Introduced the position-shift map for visualizing and disentangling MSA reconstruction errors.
  • Simulated MSAs with varying divergence levels under a defined evolutionary model.
  • Reconstructed MSAs using MAFFT and Prank, then analyzed errors with the new tools.

Main Results:

  • A high percentage (40-99%) of gapped segments in reconstructed MSAs contained errors.
  • In many erroneous cases, aligners produced MSAs with complete-likelihood scores equal to or higher than true MSAs.
  • Position-shift map analyses revealed that true MSAs are in close proximity to reconstructed MSAs for low/moderate divergences, but not for high divergences.

Conclusions:

  • Improving MSA accuracy requires strategies tailored to specific aligner types.
  • Relying on a single optimal MSA may be insufficient; exploring a distribution of likely MSAs is important.