Identifying differentially regulated subnetworks from phosphoproteomic data.
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.
Klammer
Martin
M
KINAXO Biotechnologies GmbH, Am Klopferspitz 19a, 82152 Martinsried, Germany.
Godl
Klaus
K
Tebbe
Andreas
A
Schaab
Christoph
C
D000465:Algorithms; D001499:Bayes Theorem; D020869:Gene Expression Profiling; D015233:Models, Statistical; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction