title: Combining biological networks to predict genetic interactions.
abstract: Genetic interactions define overlapping functions and compensatory pathways. In particular, synthetic sick or lethal (SSL) genetic interactions are important for understanding how an organism tolerates random mutation, i.e., genetic robustness. Comprehensive identification of SSL relationships remains far from complete in any organism, because mapping these networks is highly labor intensive. The ability to predict SSL interactions, however, could efficiently guide further SSL discovery. Toward this end, we predicted pairs of SSL genes in Saccharomyces cerevisiae by using probabilistic decision trees to integrate multiple types of data, including localization, mRNA expression, physical interaction, protein function, and characteristics of network topology. Experimental evidence demonstrated the reliability of this strategy, which, when extended to human SSL interactions, may prove valuable in discovering drug targets for cancer therapy and in identifying genes responsible for multigenic diseases.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Sharyl L
authors.initials: SL
authors.lastname: Wong
authors.forename: Lan V
authors.initials: LV
authors.lastname: Zhang
authors.forename: Amy H Y
authors.initials: AH
authors.lastname: Tong
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Li
authors.forename: Debra S
authors.initials: DS
authors.lastname: Goldberg
authors.forename: Oliver D
authors.initials: OD
authors.lastname: King
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lesage
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
authors.forename: Howard
authors.initials: H
authors.lastname: Bussey
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
mesh_terms: D000818:Animals; D030541:Databases, Genetic; D003663:Decision Trees; D005838:Genotype; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation; D010641:Phenotype