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This article is part of the supplement: The 2008 International Conference on Bioinformatics & Computational Biology (BIOCOMP'08)

Open Access Research

Reverse engineering module networks by PSO-RNN hybrid modeling

Yuji Zhang12, Jianhua Xuan2, Benildo G de los Reyes3, Robert Clarke1 and Habtom W Ressom2*

Author affiliations

1 Lombardi Comprehensive Cancer Center, Georgetown University, 4000 Reservoir Rd, Washington, DC, USA

2 Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, 4300 Wilson Blvd., Arlington, VA, USA

3 School of Biology and Ecology, University of Maine, Orono, ME 04469, USA

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Citation and License

BMC Genomics 2009, 10(Suppl 1):S15  doi:10.1186/1471-2164-10-S1-S15

Published: 7 July 2009

Abstract

Background

Inferring a gene regulatory network (GRN) from high throughput biological data is often an under-determined problem and is a challenging task due to the following reasons: (1) thousands of genes are involved in one living cell; (2) complex dynamic and nonlinear relationships exist among genes; (3) a substantial amount of noise is involved in the data, and (4) the typical small sample size is very small compared to the number of genes. We hypothesize we can enhance our understanding of gene interactions in important biological processes (differentiation, cell cycle, and development, etc) and improve the inference accuracy of a GRN by (1) incorporating prior biological knowledge into the inference scheme, (2) integrating multiple biological data sources, and (3) decomposing the inference problem into smaller network modules.

Results

This study presents a novel GRN inference method by integrating gene expression data and gene functional category information. The inference is based on module network model that consists of two parts: the module selection part and the network inference part. The former determines the optimal modules through fuzzy c-mean (FCM) clustering and by incorporating gene functional category information, while the latter uses a hybrid of particle swarm optimization and recurrent neural network (PSO-RNN) methods to infer the underlying network between modules. Our method is tested on real data from two studies: the development of rat central nervous system (CNS) and the yeast cell cycle process. The results are evaluated by comparing them to previously published results and gene ontology annotation information.

Conclusion

The reverse engineering of GRNs in time course gene expression data is a major obstacle in system biology due to the limited number of time points. Our experiments demonstrate that the proposed method can address this challenge by: (1) preprocessing gene expression data (e.g. normalization and missing value imputation) to reduce the data noise; (2) clustering genes based on gene expression data and gene functional category information to identify biologically meaningful modules, thereby reducing the dimensionality of the data; (3) modeling GRNs with the PSO-RNN method between the modules to capture their nonlinear and dynamic relationships. The method is shown to lead to biologically meaningful modules and networks among the modules.