Journal
BMC SYSTEMS BIOLOGY
Volume 4, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1752-0509-4-15
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Funding
- European Community's Seventh Framework Programme [HEALTH-F4-2007200767]
- Edmond J. Safra Bioinformatics Program at Tel Aviv University
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Background: Mathematical modeling of biological networks is an essential part of Systems Biology. Developing and using such models in order to understand gene regulatory networks is a major challenge. Results: We present an algorithm that determines the smallest perturbations required for manipulating the dynamics of a network formulated as a Petri net, in order to cause or avoid a specified phenotype. By modifying McMillan's unfolding algorithm, we handle partial knowledge and reduce computation cost. The methodology is demonstrated on a glioma network. Out of the single gene perturbations, activation of glutathione S-transferase P (GSTP1) gene was by far the most effective in blocking the cancer phenotype. Among pairs of perturbations, NFkB and TGF-beta had the largest joint effect, in accordance with their role in the EMT process. Conclusion: Our method allows perturbation analysis of regulatory networks and can overcome incomplete information. It can help in identifying drug targets and in prioritizing perturbation experiments.
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