Computational Biology abstract

Analysis abstract


Nature Biotechnology 25, 1119 - 1126 (2007)
Published online: 5 October 2007 | doi:10.1038/nbt1338

Drug—target network

Muhammed A Yi nodotldi nodotri nodotm1,2,3, Kwang-Il Goh1,4,5, Michael E Cusick1,2, Albert-László Barabási1,4,6 & Marc Vidal1,2


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.

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  1. Center for Cancer Systems Biology (CCSB), Harvard Medical School, 44 Binney St., Boston, Massachusetts 02115, USA.
  2. Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, 44 Binney St., Boston, Massachusetts 02115, USA.
  3. Division of Engineering and Applied Sciences, Harvard University, 9 Oxford St., Cambridge, Massachusetts 02138, USA.
  4. Center for Complex Network Research and Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556, USA.
  5. Department of Physics, Korea University, Seoul 136-713, Korea.
  6. Center for Complex Network Research, and the Departments of Physics, Computer Science and Biology, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, MA 02115.

Correspondence to: Albert-László Barabási1,4,6 e-mail: alb@nd.edu

Correspondence to: Marc Vidal1,2 e-mail: marc_vidal@dfci.harvard.edu



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