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Dynamical analysis of cellular networks based on the Green’s function matrix. (English) Zbl 1403.92094
Summary: The complexity of cellular networks often limits human intuition in understanding functional regulations in a cell from static network diagrams. To this end, mathematical models of ordinary differential equations (ODEs) have commonly been used to simulate dynamical behavior of cellular networks, to which a quantitative model analysis can be applied in order to gain biological insights. In this paper, we introduce a dynamical analysis based on the use of Green’s function matrix (GFM) as sensitivity coefficients with respect to initial concentrations. In contrast to the classical (parametric) sensitivity analysis, the GFM analysis gives a dynamical, molecule-by-molecule insight on how system behavior is accomplished and complementarily how (impulse) signal propagates through the network. The knowledge gained will have application from model reduction and validation to drug discovery research in identifying potential drug targets, studying drug efficacy and specificity, and optimizing drug dosing and timing. The efficacy of the method is demonstrated through applications to common network motifs and a Fas-induced programmed cell death model in Jurkat T cell line.
92C42 Systems biology, networks
92C37 Cell biology
SBML-SAT; sbtoolbox
Full Text: DOI
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