Title
Efficient Characterization of Parametric Uncertainty of Complex (Bio)chemical Networks
Abstract
Parametric uncertainty is a particularly challenging and relevant aspect of systems analysis in domains such as systems biology where, both for inference and for assessing prediction uncertainties, it is essential to characterize the system behavior globally in the parameter space. However, current methods based on local approximations or on Monte-Cario sampling cope only insufficiently with high-dimensional parameter spaces associated with complex network models. Here, we propose an alternative deterministic methodology that relies on sparse polynomial approximations. We propose a deterministic computational interpolation scheme which identifies most significant expansion coefficients adaptively. We present its performance in kinetic model equations from computational systems biology with several hundred parameters and state variables, leading to numerical approximations of the parametric solution on the entire parameter space. The scheme is based on adaptive Smolyak interpolation of the parametric solution at judiciously and adaptively chosen points in parameter space. As Monte-Cario sampling, it is "non-intrusive" and well-suited for massively parallel implementation, but affords higher convergence rates. This opens up new avenues for large-scale dynamic network analysis by enabling scaling for many applications, including parameter estimation, uncertainty quantification, and systems design.
Year
DOI
Venue
2015
10.1371/journal.pcbi.1004457
PLOS COMPUTATIONAL BIOLOGY
Field
DocType
Volume
Dynamic network analysis,Mathematical optimization,Uncertainty quantification,Computer science,Interpolation,Systems design,Parametric statistics,Modelling biological systems,State variable,Parameter space,Bioinformatics
Journal
11
Issue
ISSN
Citations 
8
1553-7358
1
PageRank 
References 
Authors
0.40
7
4
Name
Order
Citations
PageRank
claudia schillings1102.78
Mikael Sunnåker2443.02
Jörg Stelling328034.55
Christoph Schwab459558.38