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Bioinformatics Advance Access originally published online on April 23, 2008
Bioinformatics 2008 24(12):1442-1447; doi:10.1093/bioinformatics/btn200
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A global pathway crosstalk network

Yong Li *, Pankaj Agarwal and Dilip Rajagopalan

Computational Biology, GlaxoSmithKline R&D, 709 Swedeland Road, UMW2230, King of Prussia, PA 19406, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: Given the complex nature of biological systems, pathways often need to function in a coordinated fashion in order to produce appropriate physiological responses to both internal and external stimuli. Therefore, understanding the interaction and crosstalk between pathways is important for understanding the function of both cells and more complex systems.

Results: We have developed a computational approach to detect crosstalk among pathways based on protein interactions between the pathway components. We built a global mammalian pathway crosstalk network that includes 580 pathways (covering 4753 genes) with 1815 edges between pathways. This crosstalk network follows a power-law distribution: P(k) ~ k–{gamma}, {gamma} = 1.45, where P(k) is the number of pathways with k neighbors, thus pathway interactions may exhibit the same scale-free phenomenon that has been documented for protein interaction networks. We further used this network to understand colorectal cancer progression to metastasis based on transcriptomic data.

Contact: yong.2.li{at}gsk.com

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Limsoon Wong

Received on July 11, 2007; revised on April 3, 2008; accepted on April 21, 2008

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