title: OrthoList: a compendium of C. elegans genes with human orthologs.
abstract: BACKGROUND
  C. elegans is an important model for genetic studies relevant to human biology and disease. We sought to assess the orthology between C. elegans and human genes to understand better the relationship between their genomes and to generate a compelling list of candidates to streamline RNAi-based screens in this model.
  
  
  RESULTS
  We performed a meta-analysis of results from four orthology prediction programs and generated a compendium, "OrthoList", containing 7,663 C. elegans protein-coding genes. Various assessments indicate that OrthoList has extensive coverage with low false-positive and false-negative rates. Part of this evaluation examined the conservation of components of the receptor tyrosine kinase, Notch, Wnt, TGF-ß and insulin signaling pathways, and led us to update compendia of conserved C. elegans kinases, nuclear hormone receptors, F-box proteins, and transcription factors. Comparison with two published genome-wide RNAi screens indicated that virtually all of the conserved hits would have been obtained had just the OrthoList set (∼38% of the genome) been targeted. We compiled Ortholist by InterPro domains and Gene Ontology annotation, making it easy to identify C. elegans orthologs of human disease genes for potential functional analysis.
  
  
  CONCLUSIONS
  We anticipate that OrthoList will be of considerable utility to C. elegans researchers for streamlining RNAi screens, by focusing on genes with apparent human orthologs, thus reducing screening effort by ∼60%. Moreover, we find that OrthoList provides a useful basis for annotating orthology and reveals more C. elegans orthologs of human genes in various functional groups, such as transcription factors, than previously described.
authors.affiliation: Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America. ds451@columbia.edu
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Shaye
authors.forename: Iva
authors.initials: I
authors.lastname: Greenwald
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D030541:Databases, Genetic; D023281:Genomics; D006801:Humans; D058977:Molecular Sequence Annotation; D034622:RNA Interference; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D013045:Species Specificity
chemical_list: D029742:Caenorhabditis elegans Proteins