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Published online on May 14, 2007, 10.1073/pnas.0701361104
PNAS | May 22, 2007 | vol. 104 | no. 21 | 8685-8690


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PHYSICAL SCIENCES / APPLIED PHYSICAL SCIENCES
The human disease network

Kwang-Il Goh*,{dagger},{ddagger},§, Michael E. Cusick{dagger},{ddagger},¶, David Valle||, Barton Childs||, Marc Vidal{dagger},{ddagger},¶,**, and Albert-László Barabási*,{dagger},{ddagger},**

*Center for Complex Network Research and Department of Physics, University of Notre Dame, Notre Dame, IN 46556; {dagger}Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana–Farber Cancer Institute, 44 Binney Street, Boston, MA 02115; {ddagger}Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; §Department of Physics, Korea University, Seoul 136-713, Korea; and ||Department of Pediatrics and the McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Edited by H. Eugene Stanley, Boston University, Boston, MA, and approved April 3, 2007 (received for review February 14, 2007)

A network of disorders and disease genes linked by known disorder–gene associations offers a platform to explore in a single graph-theoretic framework all known phenotype and disease gene associations, indicating the common genetic origin of many diseases. Genes associated with similar disorders show both higher likelihood of physical interactions between their products and higher expression profiling similarity for their transcripts, supporting the existence of distinct disease-specific functional modules. We find that essential human genes are likely to encode hub proteins and are expressed widely in most tissues. This suggests that disease genes also would play a central role in the human interactome. In contrast, we find that the vast majority of disease genes are nonessential and show no tendency to encode hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network. A selection-based model explains the observed difference between essential and disease genes and also suggests that diseases caused by somatic mutations should not be peripheral, a prediction we confirm for cancer genes.

biological networks | complex networks | human genetics | systems biology | diseasome

Author contributions: D.V., B.C., M.V., and A.-L.B. designed research; K.-I.G. and M.E.C. performed research; K.-I.G. and M.E.C. analyzed data; and K.-I.G., M.E.C., D.V., M.V., and A.-L.B. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0701361104/DC1.

**To whom correspondence may be addressed. E-mail: alb{at}nd.edu or marc_vidal{at}dfci.harvard.edu

© 2007 by The National Academy of Sciences of the USA


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