The human disease network

Kwang Il Goh, Michael E. Cusick, David Valle, Barton Childs, Marc Vidal, Albert László Barabási

Research output: Contribution to journalArticle

2099 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8685-8690
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number21
DOIs
Publication statusPublished - 2007 May 22

Keywords

  • Biological networks
  • Complex networks
  • Diseasome
  • Human genetics
  • Systems biology

ASJC Scopus subject areas

  • General

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  • Cite this

    Goh, K. I., Cusick, M. E., Valle, D., Childs, B., Vidal, M., & Barabási, A. L. (2007). The human disease network. Proceedings of the National Academy of Sciences of the United States of America, 104(21), 8685-8690. https://doi.org/10.1073/pnas.0701361104