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Accounting for ambiguity in ancestral sequence reconstruction.

A Oliva1,2, S Pulicani1, V Lefort1

  • 1Department of Computer Science, LIRMM, CNRS & Université de Montpellier, Montpellier, France.

Bioinformatics (Oxford, England)
|April 13, 2019
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Summary

This study introduces the minimum posterior expected error (MPEE) criterion for ancestral sequence reconstruction, improving accuracy by considering uncertainty. The new method enhances understanding of molecular evolution compared to standard approaches.

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Area of Science:

  • Molecular Evolution
  • Phylogenetics
  • Bioinformatics

Background:

  • Ancestral genetic sequence reconstruction is vital for understanding molecular evolution.
  • Current methods infer ancestral states but lack information on inference uncertainty.
  • Standard criteria maximize or minimize statistical measures, overlooking uncertainty.

Purpose of the Study:

  • Introduce a novel criterion, minimum posterior expected error (MPEE), for ancestral sequence reconstruction.
  • Address the limitation of existing methods in conveying inference uncertainty.
  • Improve the accuracy and precision of reconstructing ancestral genetic sequences.

Main Methods:

  • Developed the minimum posterior expected error (MPEE) criterion.
  • Evaluated a Brier score-based criterion, independent of tuning parameters.
  • Assessed other criteria with arbitrary tuning parameters.
  • Conducted large-scale simulations to compare methods.

Main Results:

  • MPEE selects a single state when data signal is strong, and multiple states otherwise.
  • MPEE and Brier-based criteria show substantial increases in ancestral sequence inference accuracy.
  • These new criteria offer realistic compromises on solution precision.
  • Outperformed standard approaches in large-scale simulations.

Conclusions:

  • The MPEE criterion offers a significant advancement in ancestral sequence reconstruction.
  • New criteria improve accuracy by incorporating uncertainty, crucial for molecular evolution studies.
  • PhyML software implements MAP and MPEE for nucleotide and amino-acid sequences.