title: Drug-target network.
abstract: The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein-protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration-approved drugs and proteins linked by drug-target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local clustering of drugs of similar types according to Anatomical Therapeutic Chemical classification. Topological analyses of this network quantitatively showed an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins. By including drugs currently under investigation, we identified a trend toward more functionally diverse targets improving polypharmacology. To analyze the relationships between drug targets and disease-gene products, we measured the shortest distance between both sets of proteins in current models of the human interactome network. Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed.
authors.affiliation: Center for Cancer Systems Biology (CCSB), Harvard Medical School, 44 Binney St., Boston, Massachusetts 02115, USA.
authors.forename: Muhammed A
authors.initials: MA
authors.lastname: Yildirim
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Goh
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cusick
authors.forename: Albert-László
authors.initials: AL
authors.lastname: Barabási
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
mesh_terms: D003198:Computer Simulation; D016208:Databases, Factual; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D008954:Models, Biological; D015398:Signal Transduction; D049490:Systems Biology; D014481:United States; D014486:United States Food and Drug Administration