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Control of stationary behavior in probabilistic Boolean networks by means of structural intervention. (English) Zbl 1099.92003

Summary: Probabilistic Boolean Networks (PBNs) were recently introduced as models of gene regulatory networks. The dynamical behavior of PBNs, which are probabilistic generalizations of Boolean networks, can be studied using Markov chain theory. In particular, the steady-state or long-run behavior of PBNs may reflect the phenotype or functional state of the cell. Approaches to alter the steady-state behavior in a specific prescribed manner, in cases of aberrant cellular states, such as tumorigenesis, would be highly beneficial. This paper develops a methodology for altering the steady-state probabilities of certain states or sets of states with minimal modifications to the underlying rule-based structure.
This approach is framed as an optimization problem that we propose to solve using genetic algorithms, which are well suited for capturing the underlying structure of PBNs and are able to locate the optimal solution in a highly efficient manner. Several computer simulation experiments support the proposed methodology.

MSC:

92B05 General biology and biomathematics
60J20 Applications of Markov chains and discrete-time Markov processes on general state spaces (social mobility, learning theory, industrial processes, etc.)
90C59 Approximation methods and heuristics in mathematical programming
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References:

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