title: Protein-protein interactions and networks: forward and reverse edgetics.
abstract: Phenotypic variations of an organism may arise from alterations of cellular networks, ranging from the complete loss of a gene product to the specific perturbation of a single molecular interaction. In interactome networks that are modeled as nodes (macromolecules) connected by edges (interactions), these alterations can be thought of as node removal and edge-specific or "edgetic" perturbations, respectively. Here we present two complementary strategies, forward and reverse edgetics, to investigate the phenotypic outcomes of edgetic perturbations of binary protein-protein interaction networks. Both approaches are based on the yeast two-hybrid system (Y2H). The first allows the determination of the interaction profile of proteins encoded by alleles with known phenotypes to identify edgetic alleles. The second is used to directly isolate edgetic alleles for subsequent in vivo characterization.
authors.affiliation: Department of Cancer Biology, Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Charloteaux
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhong
authors.forename: Matija
authors.initials: M
authors.lastname: Dreze
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cusick
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
mesh_terms: D000483:Alleles; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D011506:Proteins