title: Comparison of eukaryotic phylogenetic profiling approaches using species tree aware methods.
abstract: BACKGROUND
  Phylogenetic profiling encompasses an important set of methodologies for in silico high throughput inference of functional relationships between genes. The simplest profiles represent the distribution of gene presence-absence in a set of species as a sequence of 0's and 1's, and it is assumed that functionally related genes will have more similar profiles. The methodology has been successfully used in numerous studies of prokaryotic genomes, although its application in eukaryotes appears problematic, with reported low accuracy due to the complex genomic organization within this domain of life. Recently some groups have proposed an alternative approach based on the correlation of homologous gene group sizes, taking into account all potentially informative genetic events leading to a change in group size, regardless of whether they result in a de novo group gain or total gene group loss.
  
  
  RESULTS
  We have compared the performance of classical presence-absence and group size based approaches using a large, diverse set of eukaryotic species. In contrast to most previous comparisons in Eukarya, we take into account the species phylogeny. We also compare the approaches using two different group categories, based on orthology and on domain-sharing. Our results confirm a limited overall performance of phylogenetic profiling in eukaryotes. Although group size based approaches initially showed an increase in performance for the domain-sharing based groups, this seems to be an overestimation due to a simplistic negative control dataset and the choice of null hypothesis rejection criteria.
  
  
  CONCLUSIONS
  Presence-absence profiling represents a more accurate classifier of related versus non-related profile pairs, when the profiles under consideration have enough information content. Group size based approaches provide a complementary means of detecting domain or family level co-evolution between groups that may be elusive to presence-absence profiling. Moreover positive correlation between co-evolution scores and functional links imply that these methods could be used to estimate functional distances between gene groups and to cluster them based on their functional relatedness. This study should have important implications for the future development and application of phylogenetic profiling methods, not only in eukaryotic, but also in prokaryotic datasets.
authors.affiliation: Laboratoire de Biologie et Génomique Intégrative, Département de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UDS, Illkirch, France. ruano@igbmc.fr
authors.forename: Valentín
authors.initials: V
authors.lastname: Ruano-Rubio
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.forename: Julie D
authors.initials: JD
authors.lastname: Thompson
mesh_terms: D019295:Computational Biology / Q000379:methods*; D056890:Eukaryota / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D008957:Models, Genetic; D010802:Phylogeny; D013045:Species Specificity