Motivation: Inherent non-linearities in biomolecular interactions make the identification of network interactions difficult. One of the principal problems is that all methods based on the use of linear time-invariant models will have fundamental limitations in their capability to infer certain non-linear network interactions. Another difficulty is the multiplicity of possible solutions, since, for a given dataset, there may be many different possible networks which generate the same time-series expression profiles.

Results: A novel algorithm for the inference of biomolecular interaction networks from temporal expression data is presented. Linear time-varying models, which can represent a much wider class of time-series data than linear time-invariant models, are employed in the algorithm. From time-series expression profiles, the model parameters are identified by solving a non-linear optimization problem. In order to systematically reduce the set of possible solutions for the optimization problem, a filtering process is performed using a phase-portrait analysis with random numerical perturbations. The proposed approach has the advantages of not requiring the system to be in a stable steady state, of using time-series profiles which have been generated by a single experiment, and of allowing non-linear network interactions to be identified. The ability of the proposed algorithm to correctly infer network interactions is illustrated by its application to three examples: a non-linear model for cAMP oscillations in Dictyostelium discoideum, the cell-cycle data for Saccharomyces cerevisiae and a large-scale non-linear model of a group of synchronized Dictyostelium cells.

Availability: The software used in this article is available from http://sbie.kaist.ac.kr/software

• PMID: 18367478
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Reference Type

Journal Article | Research Support, Non-U.S. Gov't

Authors

Kim J, Bates DG, Postlethwaite I, Heslop-Harrison P, Cho KH

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