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Bioinformatics Advance Access published online on March 16, 2006

Bioinformatics, doi:10.1093/bioinformatics/btl090
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© The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received December 5, 2005
Revised March 7, 2006
Accepted March 7, 2006

Article

An effective structure learning method for constructing gene networks

Xue-wen Chen 1 *, Gopalakrishna Anantha 1, and Xinkun Wang 2

1 Bioinformatics and Computational Life Sciences Laboratory, Electrical Engineering and Computer Science Department, 1520 West 15th Street, The University of Kansas, Lawrence, KS 66045, USA
2 Higuchi Biosciences Center, 2099 Constant Avenue, The University of Kansas, Lawrence, KS 66047, USA

* To whom correspondence should be addressed.
Xue-wen Chen, E-mail: xwchen{at}ku.edu


   Abstract

Motivation: Bayesian network methods have shown promise in gene regulatory network reconstruction because of their capability of capturing causal relationships between genes and handling data with noises found in biological experiments. The problem of learning network structures, however, is NP hard. Consequently, heuristic methods such as hill climbing are used for structure learning. For networks of a moderate size, hill climbing methods are not computationally efficient. Furthermore, relatively low accuracy of the learned structures may be observed. The purpose of this paper is to present a novel structure learning method for gene network discovery.

Results: In this paper, we present a novel structure learning method to reconstruct the underlying gene networks from the observational gene expression data. Unlike hill climbing approaches, the proposed method first constructs an undirected network based on mutual information between two nodes and then split the structure into substructures. The directional orientations for the edges that connect two nodes are then obtained by optimizing a scoring function for each substructure. Our method is evaluated using two benchmark network datasets with known structures. The results show that the proposed method can identify networks that are close to the optimal structures. It outperforms hill climbing methods in terms of both computation time and predicted structure accuracy. We also apply the method to gene expression data measured during the yeast cycle and show the effectiveness of the proposed method for network reconstruction.


Associate Editor: John Quackenbush
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[Abstract] [Full Text] [PDF]



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