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Comprehensive estimation of input signals and dynamics in biochemical reaction networks
University of Freiburg, Germany.
University of Freiburg, Germany.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
University of Freiburg, Germany.
2012 (English)In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 28, no 18, I529-I534 p.Article in journal (Refereed) Published
Abstract [en]

Motivation: Cellular information processing can be described mathematically using differential equations. Often, external stimulation of cells by compounds such as drugs or hormones leading to activation has to be considered. Mathematically, the stimulus is represented by a time-dependent input function. less thanbrgreater than less thanbrgreater thanParameters such as rate constants of the molecular interactions are often unknown and need to be estimated from experimental data, e.g. by maximum likelihood estimation. For this purpose, the input function has to be defined for all times of the integration interval. This is usually achieved by approximating the input by interpolation or smoothing of the measured data. This procedure is suboptimal since the input uncertainties are not considered in the estimation process which often leads to overoptimistic confidence intervals of the inferred parameters and the model dynamics. less thanbrgreater than less thanbrgreater thanResults: This article presents a new approach which includes the input estimation into the estimation process of the dynamical model parameters by minimizing an objective function containing all parameters simultaneously. We applied this comprehensive approach to an illustrative model with simulated data and compared it to alternative methods. Statistical analyses revealed that our method improves the prediction of the model dynamics and the confidence intervals leading to a proper coverage of the confidence intervals of the dynamic parameters. The method was applied to the JAK-STAT signaling pathway.

Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy B , 2012. Vol. 28, no 18, I529-I534 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-84533DOI: 10.1093/bioinformatics/bts393ISI: 000308532300033OAI: diva2:560167
Available from: 2012-10-12 Created: 2012-10-12 Last updated: 2014-09-10

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