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ASPEN, a methodology for reconstructing protein evolution with improved accuracy using ensemble models.

Roman Sloutsky1,2,3,4, Kristen M Naegle2,4,5,6

  • 1Program in Computational and Systems Biology, Washington University, St. Louis, United States.

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|October 18, 2019
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Summary
This summary is machine-generated.

Selecting diverse protein sequences improves evolutionary model accuracy. Reproducibility of models from subsampled data predicts accuracy, enabling better evolutionary history reconstruction.

Keywords:
computational biologydomainsensemblesevolutionary biologyhomologyhumanproteinsystems biologytrees

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Area of Science:

  • Computational Biology
  • Evolutionary Biology
  • Bioinformatics

Background:

  • Evolutionary reconstruction algorithms model protein or species evolutionary history.
  • Algorithm accuracy is sensitive to input data quality, including sequence selection and alignment.
  • Quantifying the accuracy of evolutionary models has been a persistent challenge.

Purpose of the Study:

  • To investigate if variance from subsampled sequences can identify accurate evolutionary models.
  • To develop methods for improving the accuracy of evolutionary models.
  • To assess the relationship between model reproducibility and accuracy.

Main Methods:

  • Subsampling ortholog sequences to generate multiple datasets.
  • Inferring hundreds of evolutionary models from these subsampled datasets.
  • Measuring the reproducibility of model topologies across subsamples.
  • Developing a meta-algorithm leveraging ensemble consistency for accuracy improvement.

Main Results:

  • Model reproducibility from 90% sequence subsamples directly correlates with reconstruction accuracy.
  • A measurable metric for evolutionary model accuracy was identified.
  • Topologies consistent with ensemble observations demonstrated higher accuracy.

Conclusions:

  • Subsampling and reproducibility analysis offer a novel approach to assess evolutionary model accuracy.
  • The developed meta-algorithm enhances evolutionary model accuracy by exploiting ensemble consistency.
  • This work provides a framework for more reliable evolutionary history reconstruction.