title: COCO-CL: hierarchical clustering of homology relations based on evolutionary correlations.
abstract: BACKGROUND
  Determining orthology relations among genes across multiple genomes is an important problem in the post-genomic era. Identifying orthologous genes can not only help predict functional annotations for newly sequenced or poorly characterized genomes, but can also help predict new protein-protein interactions. Unfortunately, determining orthology relation through computational methods is not straightforward due to the presence of paralogs. Traditional approaches have relied on pairwise sequence comparisons to construct graphs, which were then partitioned into putative clusters of orthologous groups. These methods do not attempt to preserve the non-transitivity and hierarchic nature of the orthology relation.
  
  
  RESULTS
  We propose a new method, COCO-CL, for hierarchical clustering of homology relations and identification of orthologous groups of genes. Unlike previous approaches, which are based on pairwise sequence comparisons, our method explores the correlation of evolutionary histories of individual genes in a more global context. COCO-CL can be used as a semi-independent method to delineate the orthology/paralogy relation for a refined set of homologous proteins obtained using a less-conservative clustering approach, or as a refiner that removes putative out-paralogs from clusters computed using a more inclusive approach. We analyze our clustering results manually, with support from literature and functional annotations. Since our orthology determination procedure does not employ a species tree to infer duplication events, it can be used in situations when the species tree is unknown or uncertain.
  
  
  BACKGROUND
  jothi@mail.nih.gov, przytyck@mail.nih.gov
  
  
  BACKGROUND
  Supplementary materials are available at Bioinformatics online.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. jothi@mail.nih.gov
authors.forename: Raja
authors.initials: R
authors.lastname: Jothi
authors.forename: Elena
authors.initials: E
authors.lastname: Zotenko
authors.forename: Asba
authors.initials: A
authors.lastname: Tasneem
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Przytycka
mesh_terms: D000465:Algorithms; D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D019143:Evolution, Molecular; D005975:Glutamate-tRNA Ligase / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D010802:Phylogeny; D021122:Protein Subunits / Q000235:genetics; D016914:Ribonuclease H / Q000235:genetics; D017385:Sequence Homology; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D021122:Protein Subunits; D012321:DNA-Directed RNA Polymerases; D016914:Ribonuclease H; D012697:Serine Endopeptidases; D005975:Glutamate-tRNA Ligase