title: Edgotype: a fundamental link between genotype and phenotype.
abstract: Classical 'one-gene/one-disease' models cannot fully reconcile with the increasingly appreciated prevalence of complicated genotype-to-phenotype associations in human disease. Genes and gene products function not in isolation but as components of intricate networks of macromolecules (DNA, RNA, or proteins) and metabolites linked through biochemical or physical interactions, represented in 'interactome' network models as 'nodes' and 'edges', respectively. Accordingly, mechanistic understanding of human disease will require understanding of how disease-causing mutations affect systems or interactome properties. The study of 'edgetics' uncovers specific loss or gain of interactions (edges) to interpret genotype-to-phenotype relationships. We review how distinct genetic variants, the genotype, lead to distinct phenotypic outcomes, the phenotype, through edgetic perturbations in interactome networks altogether representing the 'edgotype'.
authors.affiliation: Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Sahni
authors.forename: Song
authors.initials: S
authors.lastname: Yi
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhong
authors.forename: Noor
authors.initials: N
authors.lastname: Jailkhani
authors.forename: Benoit
authors.initials: B
authors.lastname: Charloteaux
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cusick
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
mesh_terms: D053263:Gene Regulatory Networks; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*