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

Authors: Sudipto Saha; Theodore Roman; Alex Galante; Mehmet Koyutürk; Robert M. Ewing

Addresses: Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio 44106, USA. ' Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA. ' School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. ' Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, Ohio 44106, USA; Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio 44106, USA. ' Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio 44106, USA

Abstract: 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.

Keywords: Wnt signalling network; eigenvector centrality; random walk; sub-networks; simulated annealing; signalling pathways; embryogenesis; differentiation; pathogenesis; colorectal cancer; protein interaction; Wnt regulatory network; Wnt signalling proteins.

DOI: 10.1504/IJCBDD.2012.049203

International Journal of Computational Biology and Drug Design, 2012 Vol.5 No.3/4, pp.185 - 205

Published online: 05 Dec 2014 *

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