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Drug—target network

Nature Biotechnology volume 25, pages 1119–1126 (2007)Cite this article

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.

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Figure 1: Distribution of drugs and drug targets.
Figure 2: Drug–target network (DT network).
Figure 3: Target-protein network (TP network) and cellular component profiles.
Figure 4: Drug targets, protein interactions and coexpression.
Figure 5: Human Disease Network and drug targets.
Figure 6: Drug targets and disease genes on human PPI network.

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Acknowledgements

We thank Andrew L. Hopkins, William G. Kaelin and the members of the M.V. and A.-L.B. laboratories and the Center for Cancer Systems Biology (CCSB), especially David E. Hill, for useful discussions. This work was supported by the Dana-Farber Cancer Institute Strategic Initiative (to M.V.), the W. M. Keck Foundation (to M.V.) and an National Institutes of Health (NIH) grant 2R01-HG001715 from the National Human Genome Research Institute and the National Institute of General Medical Sciences (to M.V. and Frederick P. Roth). K.-I.G. and A.-L.B. were supported by NIH grants IH U01 A1070499-01 and U56 CA113004 and National Science Foundation Grant ITR DMR-0926737 IIS-0513650.

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Authors and Affiliations

  1. Center for Cancer Systems Biology (CCSB), Harvard Medical School, 44 Binney St., Boston, 02115, Massachusetts, USA

    Muhammed A Yıldırım, Kwang-Il Goh, Michael E Cusick, Albert-László Barabási & Marc Vidal

  2. Department of Cancer Biology, and Department of Genetics, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, 02115, Massachusetts, USA

    Muhammed A Yıldırım, Michael E Cusick & Marc Vidal

  3. Division of Engineering and Applied Sciences, Harvard University, 9 Oxford St., Cambridge, 02138, Massachusetts, USA

    Muhammed A Yıldırım

  4. Center for Complex Network Research and Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556, USA.,

    Kwang-Il Goh & Albert-László Barabási

  5. Department of Physics, Korea University, Seoul, 136-713, Korea

    Kwang-Il Goh

  6. and the Departments of Physics, Center for Complex Network Research, Computer Science and Biology, Northeastern University, 110 Forsyth Street, 111 Dana Research Center, Boston, 02115, MA

    Albert-László Barabási

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  1. Muhammed A Yıldırım
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Corresponding authors

Correspondence to Albert-László Barabási or Marc Vidal.

Supplementary information

Supplementary Text and Figures

Supplementary Notes; Supplementary Figures 1–7 (PDF 1821 kb)

Supplementary Table 1

Curated Approved Drugs and Corresponding Targets from DrugBank database (as of March 29th 2006). (XLS 106 kb)

Supplementary Table 2

Curated Experimental Drugs and Corresponding Targets from DrugBank database (as of March 29th 2006). (XLS 121 kb)

Supplementary Table 3

Approved Drugs and Corresponding Disease and Disease Genes obtained from OMIM (as of December 21st 2005). (XLS 261 kb)

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Yıldırım, M., Goh, KI., Cusick, M. et al. Drug—target network. Nat Biotechnol 25, 1119–1126 (2007). https://doi.org/10.1038/nbt1338

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