Methodology article

Identifying differentially regulated subnetworks from phosphoproteomic data

Martin Klammer¹, Klaus Godl¹, Andreas Tebbe¹ and Christoph Schaab^1,2*

• * Corresponding author: Christoph Schaab c.schaab@kinaxo.de

Author Affiliations

¹ KINAXO Biotechnologies GmbH, Am Klopferspitz 19a, 82152 Martinsried, Germany

² Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany

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BMC Bioinformatics 2010, 11:351 doi:10.1186/1471-2105-11-351

Published: 28 June 2010

Abstract

Background

Various high throughput methods are available for detecting regulations at the level of transcription, translation or posttranslation (e.g. phosphorylation). Integrating these data with protein networks should make it possible to identify subnetworks that are significantly regulated. Furthermore, such integration can support identification of regulated entities from often noisy high throughput data. In particular, processing mass spectrometry-based phosphoproteomic data in this manner may expose signal transduction pathways and, in the case of experiments with drug-treated cells, reveal the drug's mode of action.

Results

Here, we introduce SubExtractor, an algorithm that combines phosphoproteomic data with protein network information from STRING to identify differentially regulated subnetworks and individual proteins. The method is based on a Bayesian probabilistic model combined with a genetic algorithm and rigorous significance testing. The Bayesian model accounts for information about both differential regulation and network topology. The method was tested with artificial data and subsequently applied to a comprehensive phosphoproteomics study investigating the mode of action of sorafenib, a small molecule kinase inhibitor.

Conclusions

SubExtractor reliably identifies differentially regulated subnetworks from phosphoproteomic data by integrating protein networks. The method can also be applied to gene or protein expression data.