Systems-level cancer gene identification from protein interaction network topology applied to melanogenesis-related functional genomics data

Journal of the Royal Society, Interface
T MilenkovicN Przulj


Many real-world phenomena have been described in terms of large networks. Networks have been invaluable models for the understanding of biological systems. Since proteins carry out most biological processes, we focus on analysing protein-protein interaction (PPI) networks. Proteins interact to perform a function. Thus, PPI networks reflect the interconnected nature of biological processes and analysing their structural properties could provide insights into biological function and disease. We have already demonstrated, by using a sensitive graph theoretic method for comparing topologies of node neighbourhoods called 'graphlet degree signatures', that proteins with similar surroundings in PPI networks tend to perform the same functions. Here, we explore whether the involvement of genes in cancer suggests the similarity of their topological 'signatures' as well. By applying a series of clustering methods to proteins' topological signature similarities, we demonstrate that the obtained clusters are significantly enriched with cancer genes. We apply this methodology to identify novel cancer gene candidates, validating 80 per cent of our predictions in the literature. We also validate predictions biologically by identifying cancer-r...Continue Reading


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