title: Detecting non-orthology in the COGs database and other approaches grouping orthologs using genome-specific best hits.
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.
authors.affiliation: ETH Zurich, Institute of Computational Science, CH-8092 Zürich. cdessimoz@inf.ethz.ch
authors.forename: Christophe
authors.initials: C
authors.lastname: Dessimoz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boeckmann
authors.forename: Alexander C J
authors.initials: AC
authors.lastname: Roth
authors.forename: Gaston H
authors.initials: GH
authors.lastname: Gonnet
mesh_terms: D000465:Algorithms; D030562:Databases, Protein; D019143:Evolution, Molecular; D023281:Genomics / Q000379:methods*; D010802:Phylogeny; D011506:Proteins / Q000145:classification / Q000235:genetics; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D011506:Proteins