Journal
JOURNAL OF MATHEMATICAL BIOLOGY
Volume 68, Issue 7, Pages 1757-1783Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00285-013-0685-3
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Model building of biochemical reaction networks typically involves experiments in which changes in the behavior due to natural or experimental perturbations are observed. Computational models of reaction networks are also used in a systems biology approach to study how transitions from a healthy to a diseased state result from changes in genetic or environmental conditions. In this paper we consider the nonlinear inverse problem of inferring information about the Jacobian of a Langevin type network model from covariance data of steady state concentrations associated to two different experimental conditions. Under idealized assumptions on the Langevin fluctuation matrices we prove that relative alterations in the network Jacobian can be uniquely identified when comparing the two data sets. Based on this result and the premise that alteration is locally confined to separable parts due to network modularity we suggest a computational approach using hybrid stochastic-deterministic optimization for the detection of perturbations in the network Jacobian using the sparsity promoting effect of -penalization. Our approach is illustrated by means of published metabolomic and signaling reaction networks.
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