Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 357, Issue -, Pages 245-267Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2014.06.002
Keywords
Subnetworks; Model reduction; Memory function; Protein interaction networks
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Funding
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme under REA [290038]
- BBSRC
- KCL-UCL Comprehensive Cancer Imaging Centre funding (CR-UK and EPSRC) [C1519/ A16463, C1519/A10331]
- EU [259881]
- Dimbleby Cancer Care to King's College London
- Cancer Research UK [16463] Funding Source: researchfish
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We show that in the generic situation where a biological network, e.g. a protein interaction network, is in fact a subnetwork embedded in a larger bulk network, the presence of the bulk causes not just extrinsic noise but also memory effects. This means that the dynamics of the subnetwork will depend not only on its present state, but also its past. We use projection techniques to get explicit expressions for the memory functions that encode such memory effects, for generic protein interaction networks involving binary and unary reactions such as complex formation and phosphorylation. Remarkably, in the limit of low intrinsic copy-number noise such expressions can be obtained even for nonlinear dependences on the past. We illustrate the method with examples from a protein interaction network around epidermal growth factor receptor (EGFR), which is relevant to cancer signalling. These examples demonstrate that inclusion of memory terms is not only important conceptually but also leads to substantially higher quantitative accuracy in the predicted subnetwork dynamics. (C) 2014 Elsevier Ltd. All rights reserved.
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