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Open Access Research article

Model-based extension of high-throughput to high-content data

Andrea C Pfeifer12, Daniel Kaschek3, Julie Bachmann1, Ursula Klingmüller12 and Jens Timmer34*

Author Affiliations

1 Division Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

2 Bioquant, Heidelberg University, BioQuant Building, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany

3 Physics Institute, University of Freiburg, Hermann-Herder-Strasse 3, 79104 Freiburg i.Br., Germany

4 Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Albertstrasse 19, 79104 Freiburg i.Br., Germany

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BMC Systems Biology 2010, 4:106  doi:10.1186/1752-0509-4-106

Published: 5 August 2010

Abstract

Background

High-quality quantitative data is a major limitation in systems biology. The experimental data used in systems biology can be assigned to one of the following categories: assays yielding average data of a cell population, high-content single cell measurements and high-throughput techniques generating single cell data for large cell populations. For modeling purposes, a combination of data from different categories is highly desirable in order to increase the number of observable species and processes and thereby maximize the identifiability of parameters.

Results

In this article we present a method that combines the power of high-content single cell measurements with the efficiency of high-throughput techniques. A calibration on the basis of identical cell populations measured by both approaches connects the two techniques. We develop a mathematical model to relate quantities exclusively observable by high-content single cell techniques to those measurable with high-content as well as high-throughput methods. The latter are defined as free variables, while the variables measurable with only one technique are described in dependence of those. It is the combination of data calibration and model into a single method that makes it possible to determine quantities only accessible by single cell assays but using high-throughput techniques. As an example, we apply our approach to the nucleocytoplasmic transport of STAT5B in eukaryotic cells.

Conclusions

The presented procedure can be generally applied to systems that allow for dividing observables into sets of free quantities, which are easily measurable, and variables dependent on those. Hence, it extends the information content of high-throughput methods by incorporating data from high-content measurements.