Title
Set-base dynamical parameter estimation and model invalidation for biochemical reaction networks.
Abstract
Mathematical modeling and analysis have become, for the study of biological and cellular processes, an important complement to experimental research. However, the structural and quantitative knowledge available for such processes is frequently limited, and measurements are often subject to inherent and possibly large uncertainties. This results in competing model hypotheses, whose kinetic parameters may not be experimentally determinable. Discriminating among these alternatives and estimating their kinetic parameters is crucial to improve the understanding of the considered process, and to benefit from the analytical tools at hand.In this work we present a set-based framework that allows to discriminate between competing model hypotheses and to provide guaranteed outer estimates on the model parameters that are consistent with the (possibly sparse and uncertain) experimental measurements. This is obtained by means of exact proofs of model invalidity that exploit the polynomial/rational structure of biochemical reaction networks, and by making use of an efficient strategy to balance solution accuracy and computational effort.The practicability of our approach is illustrated with two case studies. The first study shows that our approach allows to conclusively rule out wrong model hypotheses. The second study focuses on parameter estimation, and shows that the proposed method allows to evaluate the global influence of measurement sparsity, uncertainty, and prior knowledge on the parameter estimates. This can help in designing further experiments leading to improved parameter estimates.
Year
DOI
Venue
2010
10.1186/1752-0509-4-69
BMC systems biology
Keywords
Field
DocType
signal transduction,algorithms,bioinformatics,systems biology
Computer science,Systems biology,Bioinformatics,Estimation theory,Semidefinite programming,Biochemical Phenomena
Journal
Volume
Issue
ISSN
4
1
1752-0509
Citations 
PageRank 
References 
26
0.97
12
Authors
5
Name
Order
Citations
PageRank
Philipp Rumschinski1372.60
Steffen Borchers2493.28
Sandro Bosio3757.28
Robert Weismantel496490.05
Rolf Findeisen532447.45