Detecting non-orthology in the COGs database and other approaches grouping orthologs using genome-specific best hits

Nucleic Acids Res. 2006 Jul 11;34(11):3309-16. doi: 10.1093/nar/gkl433. Print 2006.

Abstract

Correct orthology assignment is a critical prerequisite of numerous comparative genomics procedures, such as function prediction, construction of phylogenetic species trees and genome rearrangement analysis. We present an algorithm for the detection of non-orthologs that arise by mistake in current orthology classification methods based on genome-specific best hits, such as the COGs database. The algorithm works with pairwise distance estimates, rather than computationally expensive and error-prone tree-building methods. The accuracy of the algorithm is evaluated through verification of the distribution of predicted cases, case-by-case phylogenetic analysis and comparisons with predictions from other projects using independent methods. Our results show that a very significant fraction of the COG groups include non-orthologs: using conservative parameters, the algorithm detects non-orthology in a third of all COG groups. Consequently, sequence analysis sensitive to correct orthology assignments will greatly benefit from these findings.

Publication types

  • Validation Study

MeSH terms

  • Algorithms*
  • Databases, Protein*
  • Evolution, Molecular
  • Genomics / methods*
  • Phylogeny
  • Proteins / classification
  • Proteins / genetics
  • Sequence Alignment
  • Sequence Analysis, Protein

Substances

  • Proteins