Low duplicability and network fragility of cancer genes

Rambaldi, Davide; Giorgi, Federico M.; Capuani, Fabrizio; Ciliberto, Andrea; Ciccarelli, Francesca D.

doi:10.1016/j.tig.2008.06.003

Cited by 63 publications

(80 citation statements)

References 22 publications

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“…Although network topology-based properties such as hubs and modules are commonly used to identify disease genes (41)(42)(43)(44), the controllability perspective provides a complementary network analysis framework for network medicine. In particular, type-II nodes that are not distinguishable from existing network properties and without publications bias were still identified by our controllability framework as nodes of special interest.…”

Section: Discussionmentioning

confidence: 99%

Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets

Vinayagam

Gibson

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

235

242

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The protein-protein interaction (PPI) network is crucial for cellular information processing and decision-making. With suitable inputs, PPI networks drive the cells to diverse functional outcomes such as cell proliferation or cell death. Here, we characterize the structural controllability of a large directed human PPI network comprising 6,339 proteins and 34,813 interactions. This network allows us to classify proteins as "indispensable," "neutral," or "dispensable," which correlates to increasing, no effect, or decreasing the number of driver nodes in the network upon removal of that protein. We find that 21% of the proteins in the PPI network are indispensable. Interestingly, these indispensable proteins are the primary targets of disease-causing mutations, human viruses, and drugs, suggesting that altering a network's control property is critical for the transition between healthy and disease states. Furthermore, analyzing copy number alterations data from 1,547 cancer patients reveals that 56 genes that are frequently amplified or deleted in nine different cancers are indispensable. Among the 56 genes, 46 of them have not been previously associated with cancer. This suggests that controllability analysis is very useful in identifying novel disease genes and potential drug targets.network biology | controllability | protein-protein interaction network | disease genes | drug targets

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Section: Discussionmentioning

confidence: 99%

Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets

Vinayagam

Gibson

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

235

242

View full text Add to dashboard Cite

show abstract

“…Indeed, ample examples of gene diversification following duplication have been described and "gene duplicability," by which we mean the ability of genes to be preserved in a population following duplication, has been extensively studied (Davis and Petrov, 2004;Koonin et al, 2004;He and Zhang, 2006;Liang et al, 2008;Rambaldi et al, 2008;Makino et al, 2009;Woods et al, 2013). Studies published on a large array of species seem to converge on the idea that some duplicated genes are more likely to be preserved in a population, and as such to potentially contribute to functional innovation, than other genes.…”

Section: Introductionmentioning

confidence: 99%

Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms

et al. 2016

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“…Going a step further in the reasoning, it has been hypothesized that mutations affecting these proteins should be particularly related to the insurgence of diseases. Some experimental validation of this prediction has been indeed obtained: Rambaldi and his group (Rambaldi D. et al, 2008) provided evidence that virtually all proteins having a degree higher than 80 in the human protein-protein interaction network are target of known cancer-related mutations. Similarly, Ortutay and Vihinen (Ortutay C. & Vihinen M. et al, 2009), after building an interaction network comprising all human proteins involved in immune response, found that the network hubs include known disease-causing genes as well as 26 new genes related to primary immunodeficiency.…”

Section: The Structure Of Protein Network: Hubsmentioning

confidence: 85%