Comparative genomics approaches accurately predict deleterious variants in plants

Thomas Kono, Li Lei, Ching Hua Shih, Paul J. Hoffman, Peter L Morrell, Justin C. Fay

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Recent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910 Arabidopsis thaliana mutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted in A. thaliana and likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.

Original languageEnglish (US)
Pages (from-to)3321-3329
Number of pages9
JournalG3: Genes, Genomes, Genetics
Volume8
Issue number10
DOIs
StatePublished - Oct 1 2018

Bibliographical note

Funding Information:
We thank members of the Morrell Lab for discussion and software testing. We also would like to thank Drs. Danelle Seymour and Karl Schmid for helpful comments on an earlier version of the manuscript. Hardware and software support were provided by the University of Minnesota Supercomputing Institute. This work was supported by the US National Science Foundation Plant Genome Program grant (DBI-1339393 to JCF and PLM), the US Department of Agriculture Biotechnology Risk Assessment Research Grants Program (BRAG) (USDA BRAG 2015-06504 to PLM), and a University of Minnesota Doctoral Dissertation Fellowship (to TJYK).

Publisher Copyright:
Copyright © 2018 Reid et al.

Keywords

  • Deleterious
  • Genome
  • Mutations
  • Phenotypes
  • Training set

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