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ABSTRACT: We proposed a scheme to infer gene regulatory networks from multiple time course gene expression datasets. As the scarcity of time course data, most current methods usually making the inferred gene regulatory network structure as an ill-posed one, and typically cannot handle multiple experimental datasets directly. On the other hand, gene expression data generated by different groups worldwide are increasingly accumulated. In this paper, we first formulate the inference of sparse and stable gene regulatory networks as a constraint optimization problem, which can be easily solved by a given single dataset. Then, two methods of network combination are proposed, which can combine structures inferred from various experimental datasets. After that, the parameters in gene regulatory network with that structure are estimated by solving another optimization problem. Finally, we test and validate our methods on synthetic datasets in a series of numerical experiments in terms of the structure accuracy and the model error.
Systems Biology (ISB), 2011 IEEE International Conference on; 10/2011
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ABSTRACT: Reconstruction of a biological system from its experimental time series data is a challenging task in systems biology. The S-system which consists of a group of nonlinear ordinary differential equations (ODEs) is an effective model to characterize molecular biological systems and analyze the system dynamics. However, inference of S-systems without the knowledge of system structure is not a trivial task due to its nonlinearity and complexity. In this paper, a pruning separable parameter estimation algorithm (PSPEA) is proposed for inferring S-systems. This novel algorithm combines the separable parameter estimation method (SPEM) and a pruning strategy, which includes adding an l₁ regularization term to the objective function and pruning the solution with a threshold value. Then, this algorithm is combined with the continuous genetic algorithm (CGA) to form a hybrid algorithm that owns the properties of these two combined algorithms. The performance of the pruning strategy in the proposed algorithm is evaluated from two aspects: the parameter estimation error and structure identification accuracy. The results show that the proposed algorithm with the pruning strategy has much lower estimation error and much higher identification accuracy than the existing method.
IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM 09/2011; 9(4):955-65. · 2.25 Impact Factor
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ABSTRACT: Clustering periodically expressed genes from their time-course expression data could help understand the molecular mechanism of those biological processes. In this paper, we propose a nonlinear model-based clustering method for periodically expressed gene profiles. As periodically expressed genes are associated with periodic biological processes, the proposed method naturally assumes that a periodically expressed gene dataset is generated by a number of periodical processes. Each periodical process is modelled by a linear combination of trigonometric sine and cosine functions in time plus a Gaussian noise term. A two stage method is proposed to estimate the model parameter, and a relocation-iteration algorithm is employed to assign each gene to an appropriate cluster. A bootstrapping method and an average adjusted Rand index (AARI) are employed to measure the quality of clustering. One synthetic dataset and two biological datasets were employed to evaluate the performance of the proposed method. The results show that our method allows the better quality clustering than other clustering methods (e.g., k-means) for periodically expressed gene data, and thus it is an effective cluster analysis method for periodically expressed gene data.
TheScientificWorldJOURNAL 01/2011; 11:2051-61. · 1.66 Impact Factor
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ABSTRACT: Several methods have been proposed to infer gene regulatory networks from time course gene expression data. As the number of genes is much larger than the number of time points at which gene expression (mRNA concentration) is measured, most existing methods need some ad hoc assumptions to infer a unique gene regulatory network from time course gene expression data. It is well known that gene regulatory networks are sparse and stable. However, inferred network from most existing methods may not be stable. In this paper we propose a method to infer sparse and stable gene regulatory networks from time course gene expression data. Instead of ad hoc assumption, we formulate the inference of sparse and stable gene regulatory networks as constraint optimization problems, which can be easily solved. To investigate the performance of our proposed method, computational experiments are conducted on synthetic datasets.
Engineering in Medicine and Biology Society (EMBC), 2010 Annual International Conference of the IEEE; 10/2010
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2010 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2010, Hong Kong, China, 18 - 21 December 2010, Proceedings; 01/2010
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[show abstract]
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ABSTRACT: Several methods have been proposed to infer gene regulatory networks from time course gene expression data. As the number of genes is much larger than the number of time points at which gene expression (mRNA concentration) is measured, most existing methods need some ad hoc assumptions to infer a unique gene regulatory network from time course gene expression data. It is well known that gene regulatory networks are sparse and stable. However, inferred network from most existing methods may not be stable. In this paper we propose a method to infer sparse and stable gene regulatory networks from time course gene expression data. Instead of ad hoc assumption, we formulate the inference of sparse and stable gene regulatory networks as constraint optimization problems, which can be easily solved. To investigate the performance of our proposed method, computational experiments are conducted on synthetic datasets.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2010; 2010:795-8.
