title: The Core Diseasome.
abstract: Large amounts of protein-protein 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.
authors: Department of Computing, Imperial College London, London, SW7 2AZ, UK. natasha@imperial.ac.uk
authors: Vuk
authors: V
authors: Janjić
authors: Nataša
authors: N
authors: Pržulj
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics; D001424:Bacterial Infections / Q000235:genetics; D016000:Cluster Analysis; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D049490:Systems Biology / Q000379:methods* / Q000706:statistics & numerical data; D014777:Virus Diseases / Q000235:genetics
chemical_list: D011506:Proteins