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Nucleic Acids Res. 2011 Feb;39(3):795-807. doi: 10.1093/nar/gkq784. Epub 2010 Sep 24.

Investigating the predictability of essential genes across distantly related organisms using an integrative approach.

Author information

1
Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.

Erratum in

  • Nucleic Acids Res. 2012 Sep;40(16):8198.

Abstract

Rapid and accurate identification of new essential genes in under-studied microorganisms will significantly improve our understanding of how a cell works and the ability to re-engineer microorganisms. However, predicting essential genes across distantly related organisms remains a challenge. Here, we present a machine learning-based integrative approach that reliably transfers essential gene annotations between distantly related bacteria. We focused on four bacterial species that have well-characterized essential genes, and tested the transferability between three pairs among them. For each pair, we trained our classifier to learn traits associated with essential genes in one organism, and applied it to make predictions in the other. The predictions were then evaluated by examining the agreements with the known essential genes in the target organism. Ten-fold cross-validation in the same organism yielded AUC scores between 0.86 and 0.93. Cross-organism predictions yielded AUC scores between 0.69 and 0.89. The transferability is likely affected by growth conditions, quality of the training data set and the evolutionary distance. We are thus the first to report that gene essentiality can be reliably predicted using features trained and tested in a distantly related organism. Our approach proves more robust and portable than existing approaches, significantly extending our ability to predict essential genes beyond orthologs.

PMID:
20870748
PMCID:
PMC3035443
DOI:
10.1093/nar/gkq784
[Indexed for MEDLINE]
Free PMC Article

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