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Frontiers of Electrical and Electronic Engineering

ISSN 2095-2732

ISSN 2095-2740(Online)

CN 10-1028/TM

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Front Elect Electr Eng    2012, Vol. 7 Issue (4) : 357-366    https://doi.org/10.1007/s11460-012-0207-x
RESEARCH ARTICLE
Co-regulated gene module detection for time series gene expression data
Wanwan TANG(), Rui LI, Shao LI, Yanda LI
MOE Key Laboratory of Bioinformatics, Bioinformatics Division, Tsinghua National Laboratory of Information Science and Technology / Department of Automation, Tsinghua University, Beijing 100084, China
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Abstract

It is important to detect interaction effect of multiple genes during certain biological process. In this paper, we proposed, from systems biology perspective, the concept of co-regulated gene module, which consists of genes that are regulated by the same regulator(s). Given a time series gene expression data, a hidden Markov model-based Bayesian model was developed to calculate the likelihood of the observed data, assuming the co-regulated gene modules are known. We further developed a Gibbs sampling strategy that is integrated with reversible jump Markov chain Monte Carlo to obtain the posterior probabilities of the co-regulated gene modules. Simulation study validated the proposed method. When compared with two existing methods, the proposed approach significantly outperformed the conventional methods.
Keywords co-regulated gene module      Bayesian      hidden Markov model      Markov chain Monte Carlo     
Corresponding Author(s): TANG Wanwan,Email:tww05@mails.tsinghua.edu.cn   
Issue Date: 05 December 2012
 Cite this article:   
Wanwan TANG,Rui LI,Shao LI, et al. Co-regulated gene module detection for time series gene expression data[J]. Front Elect Electr Eng, 2012, 7(4): 357-366.
 URL:  
https://academic.hep.com.cn/fee/EN/10.1007/s11460-012-0207-x
https://academic.hep.com.cn/fee/EN/Y2012/V7/I4/357
Fig.1  Relationship between genes and their regulators. Regulated genes are contained in CrGMs and the unregulated ones are outside the modules. Each CrGM has a hidden regulator.
Fig.1  Relationship between genes and their regulators. Regulated genes are contained in CrGMs and the unregulated ones are outside the modules. Each CrGM has a hidden regulator.
Fig.1  Relationship between genes and their regulators. Regulated genes are contained in CrGMs and the unregulated ones are outside the modules. Each CrGM has a hidden regulator.
Fig.1  Relationship between genes and their regulators. Regulated genes are contained in CrGMs and the unregulated ones are outside the modules. Each CrGM has a hidden regulator.
Fig.1  Relationship between genes and their regulators. Regulated genes are contained in CrGMs and the unregulated ones are outside the modules. Each CrGM has a hidden regulator.
Fig.2  Relationship between increments of genes and states of the regulator in a CrGM in certain biologic process
Fig.2  Relationship between increments of genes and states of the regulator in a CrGM in certain biologic process
Fig.2  Relationship between increments of genes and states of the regulator in a CrGM in certain biologic process
Fig.2  Relationship between increments of genes and states of the regulator in a CrGM in certain biologic process
Fig.2  Relationship between increments of genes and states of the regulator in a CrGM in certain biologic process
modelordernumber of genesnumber of CrGMsnumber of genes in CrGM 1number of genes in CrGM 2
Model 11202510
Model 211002510
Model 32202510
Model 421002510
Tab.1  Four time series microarray models with different characteristics
modelCrGMordertransition matrix
Model 1 / 2CrGM 11[0100.050.050.90.90.050.05]
CrGM 21[0.050.90.051/31/31/30.90.050.05]
Model 3 / 4CrGM 12[0.90.050.051/31/31/30.050.050.91/31/31/30.050.90.051/31/31/30.90.050.051/31/31/30.050.050.9]
CrGM 22[1/31/31/30.050.90.051/31/31/30.050.050.91/31/31/30.90.050.051/31/31/30.050.90.051/31/31/3]
Tab.2  Transition matrices
state value123
CrGM 1Gene 1-0.40.80
Gene 20.80.40
Gene 30.4-0.4-0.8
Gene 40-0.40.8
Gene 50.80.6-0.8
CrGM 2Gene 11.40.2-1.4
Gene 20.61.20.6,
Gene 31.2-1-1.4
Gene 4-1-1.2-0.2
Gene 5-0.2-0.61.2
Gene 6-0.2-1-1.4
Gene 7-1-1.41
Gene 8-1.40.6-0.2
Gene 9-10.6-0.6
Gene 10-1.20.21.2
Tab.3  Mean of the Gaussian distribution for emission matrices
Fig.3  Posterior probabilities of genes that belong to certain modules. For each time series microarray models, the posterior probabilities of genes that belong to CrGMs are plotted. Posterior probabilities of all the other genes are all zero. For all the four models, counting backward in the gene list, the 1st to the 10th genes are in the same CrGM and the 11th to the 15th genes are in the same CrGM. (a) Model 1; (b) Model 2; (c) Model 3; (d) Model 4.
Fig.3  Posterior probabilities of genes that belong to certain modules. For each time series microarray models, the posterior probabilities of genes that belong to CrGMs are plotted. Posterior probabilities of all the other genes are all zero. For all the four models, counting backward in the gene list, the 1st to the 10th genes are in the same CrGM and the 11th to the 15th genes are in the same CrGM. (a) Model 1; (b) Model 2; (c) Model 3; (d) Model 4.
Fig.3  Posterior probabilities of genes that belong to certain modules. For each time series microarray models, the posterior probabilities of genes that belong to CrGMs are plotted. Posterior probabilities of all the other genes are all zero. For all the four models, counting backward in the gene list, the 1st to the 10th genes are in the same CrGM and the 11th to the 15th genes are in the same CrGM. (a) Model 1; (b) Model 2; (c) Model 3; (d) Model 4.
Fig.3  Posterior probabilities of genes that belong to certain modules. For each time series microarray models, the posterior probabilities of genes that belong to CrGMs are plotted. Posterior probabilities of all the other genes are all zero. For all the four models, counting backward in the gene list, the 1st to the 10th genes are in the same CrGM and the 11th to the 15th genes are in the same CrGM. (a) Model 1; (b) Model 2; (c) Model 3; (d) Model 4.
Fig.3  Posterior probabilities of genes that belong to certain modules. For each time series microarray models, the posterior probabilities of genes that belong to CrGMs are plotted. Posterior probabilities of all the other genes are all zero. For all the four models, counting backward in the gene list, the 1st to the 10th genes are in the same CrGM and the 11th to the 15th genes are in the same CrGM. (a) Model 1; (b) Model 2; (c) Model 3; (d) Model 4.
Fig.4  Comparison of CrgMODE, -means, and WGCNA.
Fig.4  Comparison of CrgMODE, -means, and WGCNA.
Fig.4  Comparison of CrgMODE, -means, and WGCNA.
Fig.4  Comparison of CrgMODE, -means, and WGCNA.
Fig.4  Comparison of CrgMODE, -means, and WGCNA.
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