Boolean modeling techniques for protein co-expression networks in systems medicine

ABSTRACT

Introduction: Application of systems biology/systems medicine approaches is promising for proteomics/biomedical research, but requires selection of an adequate modeling type.

Areas covered: This article reviews the existing Boolean network modeling approaches, which provide in comparison with alternative modeling techniques several advantages for the processing of proteomics data. Application of methods for inference, reduction and validation of protein co-expression networks that are derived from quantitative high-throughput proteomics measurements is presented. It’s also shown how Boolean models can be used to derive system-theoretic characteristics that describe both the dynamical behavior of such networks as a whole and the properties of different cell states (e.g. healthy or diseased cell states). Furthermore, application of methods derived from control theory is proposed in order to simulate the effects of therapeutic interventions on such networks, which is a promising approach for the computer-assisted discovery of biomarkers and drug targets. Finally, the clinical application of Boolean modeling analyses is discussed.

Expert commentary: Boolean modeling of proteomics data is still in its infancy. Progress in this field strongly depends on provision of a repository with public access to relevant reference models. Also required are community supported standards that facilitate input of both proteomics and patient related data (e.g. age, gender, laboratory results, etc.).

KEYWORDS:

• Boolean networks
• control of Boolean networks
• logical models
• protein co-expression
• drug target discovery
• systems medicine
• network biomarkers
• system theoretic characteristics

Acknowledgements

We are grateful to Julian Uszkoreit for thorough proofreading and valuable discussions.

Financial & competing interests disclosure

G Mayer and M Kohl are funded by the BMBF grant de.NBI - German Network for Bioinformatics Infrastructure (FKZ 031 A 534A). The funding of M Eisenacher is related to PURE and VALIBIO, projects of Northrhine-Westphalia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.