unraveling the design principle for motif organization in signaling networks揭示主题组织信号网络的设计原则.pdfVIP

Unraveling the Design Principle for Motif Organization in Signaling Networks Samrat Chatterjee, Dhiraj Kumar* Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India Abstract Cellular signaling networks display complex architecture. Defining the design principle of this architecture is crucial for our understanding of various biological processes. Using a mathematical model for three-node feed-forward loops, we identify that the organization of motifs in specific manner within the network serves as an important regulator of signal processing. Further, incorporating a systemic stochastic perturbation to the model we could propose a possible design principle, for higher-order organization of motifs into larger networks in order to achieve specific biological output. The design principle was then verified in a large, complex human cancer signaling network. Further analysis permitted us to classify signaling nodes of the network into robust and vulnerable nodes as a result of higher order motif organization. We show that distribution of these nodes within the network at strategic locations then provides for the range of features displayed by the signaling network. Citation: Chatterjee S, Kumar D (2011) Unraveling the Design Principle for Motif Organization in Signaling Networks. PLoS ONE 6(12): e28606. doi:10.1371/ journal.pone.0028606 Editor: Christina Chan, Michigan State University, United States of America Received July 22, 2011; Accepted November 11, 2011; Published December 2, 2011 Copyright: 2011 Chatterjee, Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by the IYB