Discovery of regulatory interactions through perturbation: inference and experimental design.
We present two methods to be used interactively to infer a genetic network from gene expression measurements. The predictor method determines the set of Boolean networks consistent with an observed set of steady-state gene expression profiles, each generated from a different perturbation to the genetic network. The chooser method uses an entropy-based approach to propose an additional perturbation experiment to discriminate among the set of hypothetical networks determined by the predictor. These methods may be used iteratively and interactively to successively refine the genetic network: at each iteration, the perturbation selected by the chooser is experimentally performed to generate a new gene expression profile, and the predictor is used to derive a refined set of hypothetical gene networks using the cumulative expression data. Performance of the predictor and chooser is evaluated on simulated networks with varying number of genes and number of interactions per gene.
Ideker
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Department of Molecular Biotechnology, University of Washington, Seattle 98195-7730, USA. trunk@u.washington.edu
Thorsson
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Karp
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D000465:Algorithms; D003198:Computer Simulation; D005069:Evaluation Studies as Topic; D015870:Gene Expression; D008957:Models, Genetic