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  4. Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction
 
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Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction
File(s)
Cascades15.pdf (780.11 KB)
Accepted version
20160409.full.pdf (652.17 KB)
Published version
Author(s)
Beguerisse Diaz, M
Desikan, R
Barahona, M
Type
Journal Article
Abstract
Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal-gain cascades (i.e., when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction.
Date Issued
2016-08-31
Date Acceptance
2016-08-05
Citation
Journal of the Royal Society Interface, 2016, 13 (121)
URI
http://hdl.handle.net/10044/1/38843
DOI
https://www.dx.doi.org/10.1098/rsif.2016.0409
ISSN
1742-5689
Publisher
Royal Society, The
Journal / Book Title
Journal of the Royal Society Interface
Volume
13
Issue
121
Copyright Statement
© 2016 The Authors.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
License URL
http://creativecommons.org/licenses/by/4.0/
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Engineering & Physical Science Research Council (EPSRC)
James S. McDonnell Foundation
Engineering & Physical Science Research Council (EPSRC)
Grant Number
BB/G020434/1
EP/I017267/1
220020349
EP/N014529/1
Subjects
q-bio.MN
q-bio.MN
math.DS
math.OC
q-bio.QM
Notes
18 pages, 6 figures
Publication Status
Published
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