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Open Access Methodology article

Identification of models of heterogeneous cell populations from population snapshot data

Jan Hasenauer1*, Steffen Waldherr1, Malgorzata Doszczak2, Nicole Radde1, Peter Scheurich2 and Frank Allgöwer1

Author Affiliations

1 Institute for Systems Theory and Automatic Control, University of Stuttgart, Germany

2 Institute of Cell Biology and Immunology, University of Stuttgart, Germany

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BMC Bioinformatics 2011, 12:125  doi:10.1186/1471-2105-12-125

Published: 28 April 2011

Abstract

Background

Most of the modeling performed in the area of systems biology aims at achieving a quantitative description of the intracellular pathways within a "typical cell". However, in many biologically important situations even clonal cell populations can show a heterogeneous response. These situations require study of cell-to-cell variability and the development of models for heterogeneous cell populations.

Results

In this paper we consider cell populations in which the dynamics of every single cell is captured by a parameter dependent differential equation. Differences among cells are modeled by differences in parameters which are subject to a probability density. A novel Bayesian approach is presented to infer this probability density from population snapshot data, such as flow cytometric analysis, which do not provide single cell time series data. The presented approach can deal with sparse and noisy measurement data. Furthermore, it is appealing from an application point of view as in contrast to other methods the uncertainty of the resulting parameter distribution can directly be assessed.

Conclusions

The proposed method is evaluated using artificial experimental data from a model of the tumor necrosis factor signaling network. We demonstrate that the methods are computationally efficient and yield good estimation result even for sparse data sets.