Network-based approaches for extending the Wnt signalling pathway and identifying context-specific sub-networks

Wnt signalling is a critically important signalling pathway regulating embryogenesis and differentiation, and is broadly conserved amongst multicellular animals. In addition, dysregulation of Wnt signalling contributes to the pathogenesis of many human cancers, in particular colorectal cancer. Core members of the Wnt signalling pathway are quite well defined, although it has become apparent that a much broader network of interacting proteins regulates Wnt signalling activity. The goal of this paper is first to identify novel members of the Wnt regulatory network; and second, to identify sub-networks of the larger Wnt signalling network that are active in different biological contexts. We address these two questions using complementary computational approaches and show how these approaches may identify potentially novel Wnt signalling proteins as well as defining Wnt sub-networks active in different stages of colorectal cancer.