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Issue 10, 2012
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The Core Diseasome

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Abstract

Large amounts of proteinprotein interaction (PPI) data are available. The human PPI network currently contains over 56 000 interactions between 11 100 proteins. It has been demonstrated that the structure of this network is not random and that the same wiring patterns in it underlie the same biological processes and diseases. In this paper, we ask if there exists a subnetwork of the human PPI network such that its topology is the key to disease formation and hence should be the primary object of therapeutic intervention. We demonstrate that such a subnetwork exists and can be obtained purely computationally. In particular, by successively pruning the entire human PPI network, we are left with a “core” subnetwork that is not only topologically and functionally homogeneous, but is also enriched in disease genes, drug targets, and it contains genes that are known to drive disease formation. We call this subnetwork the Core Diseasome. Furthermore, we show that the topology of the Core Diseasome is unique in the human PPI network suggesting that it may be the wiring of this network that governs the mutagenesis that leads to disease. Explaining the mechanisms behind this phenomenon and exploiting them remains a challenge.

Graphical abstract: The Core Diseasome

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Publication details

The article was received on 21 Mar 2012, accepted on 04 Jul 2012 and first published on 06 Jul 2012


Article type: Paper
DOI: 10.1039/C2MB25230A
Citation: Mol. BioSyst., 2012,8, 2614-2625
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    The Core Diseasome

    V. Janjić and N. Pržulj, Mol. BioSyst., 2012, 8, 2614
    DOI: 10.1039/C2MB25230A

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