title: Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiae gene function.
abstract: BACKGROUND
  Learning the function of genes is a major goal of computational genomics. Methods for inferring gene function have typically fallen into two categories: 'guilt-by-profiling', which exploits correlation between function and other gene characteristics; and 'guilt-by-association', which transfers function from one gene to another via biological relationships.
  
  
  RESULTS
  We have developed a strategy ('Funckenstein') that performs guilt-by-profiling and guilt-by-association and combines the results. Using a benchmark set of functional categories and input data for protein-coding genes in Saccharomyces cerevisiae, Funckenstein was compared with a previous combined strategy. Subsequently, we applied Funckenstein to 2,455 Gene Ontology terms. In the process, we developed 2,455 guilt-by-profiling classifiers based on 8,848 gene characteristics and 12 functional linkage graphs based on 23 biological relationships.
  
  
  CONCLUSIONS
  Funckenstein outperforms a previous combined strategy using a common benchmark dataset. The combination of 'guilt-by-profiling' and 'guilt-by-association' gave significant improvement over the component classifiers, showing the greatest synergy for the most specific functions. Performance was evaluated by cross-validation and by literature examination of the top-scoring novel predictions. These quantitative predictions should help prioritize experimental study of yeast gene functions.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
authors.forename: Lan V
authors.initials: LV
authors.lastname: Zhang
authors.forename: Murat
authors.initials: M
authors.lastname: Taşan
authors.forename: Francis D
authors.initials: FD
authors.lastname: Gibbons
authors.forename: Oliver D
authors.initials: OD
authors.lastname: King
authors.forename: Julie
authors.initials: J
authors.lastname: Park
authors.forename: Zeba
authors.initials: Z
authors.lastname: Wunderlich
authors.forename: J Michael
authors.initials: JM
authors.lastname: Cherry
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D005800:Genes, Fungal; D053858:Metabolic Networks and Pathways; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D012984:Software
chemical_list: D029701:Saccharomyces cerevisiae Proteins