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Ninth Annual IEEE International Conference on Pervasive Computing and Communications, PerCom 2011, 21-25 March 2011, Seattle, WA, USA, Workshop Proceedings; 01/2011
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IEEE 1st International Conference on Computational Advances in Bio and Medical Sciences, ICCABS 2011, Orlando, FL, USA, February 3-5, 2011; 01/2011
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Proceedings of the ISCA 3rd International Conference on Bioinformatics and Computational Biology, BICoB-2011, March 23-25, 2011, Holiday Inn Downtown-Superdome, New Orleans, Louisiana, USA; 01/2011
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ABSTRACT: Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold that defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we propose a new inference algorithm that incorporates mutual information (MI), conditional mutual information (CMI), and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm is evaluated using both synthetic time series data sets and a biological time series data set (Saccharomyces cerevisiae). The results show that the proposed algorithm produced fewer false edges and significantly improved the precision when compared to existing MDL algorithm.
Advances in experimental medicine and biology 01/2011; 696:37-43. · 1.09 Impact Factor
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Proceedings of the First ACM International Conference on Bioinformatics and Computational Biology, BCB 2010, Niagara Falls, NY, USA, August 2-4, 2010; 01/2010
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ABSTRACT: A number of models and algorithms have been proposed in the past for gene regulatory network (GRN) inference; however, none of them address the effects of the size of time-series microarray expression data in terms of the number of time-points. In this paper, we study this problem by analyzing the behaviour of three algorithms based on information theory and dynamic Bayesian network (DBN) models. These algorithms were implemented on different sizes of data generated by synthetic networks. Experiments show that the inference accuracy of these algorithms reaches a saturation point after a specific data size brought about by a saturation in the pair-wise mutual information (MI) metric; hence there is a theoretical limit on the inference accuracy of information theory based schemes that depends on the number of time points of micro-array data used to infer GRNs. This illustrates the fact that MI might not be the best metric to use for GRN inference algorithms. To circumvent the limitations of the MI metric, we introduce a new method of computing time lags between any pair of genes and present the pair-wise time lagged Mutual Information (TLMI) and time lagged Conditional Mutual Information (TLCMI) metrics. Next we use these new metrics to propose novel GRN inference schemes which provides higher inference accuracy based on the precision and recall parameters.
It was observed that beyond a certain number of time-points (i.e., a specific size) of micro-array data, the performance of the algorithms measured in terms of the recall-to-precision ratio saturated due to the saturation in the calculated pair-wise MI metric with increasing data size. The proposed algorithms were compared to existing approaches on four different biological networks. The resulting networks were evaluated based on the benchmark precision and recall metrics and the results favour our approach.
To alleviate the effects of data size on information theory based GRN inference algorithms, novel time lag based information theoretic approaches to infer gene regulatory networks have been proposed. The results show that the time lags of regulatory effects between any pair of genes play an important role in GRN inference schemes.
BMC Bioinformatics 01/2010; 11 Suppl 6:S19. · 2.75 Impact Factor
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ABSTRACT: Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold which defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we proposed a new inference algorithm which incorporated mutual information (MI), conditional mutual information (CMI) and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter.
The performance of the proposed algorithm was evaluated using both synthetic time series data sets and a biological time series data set for the yeast Saccharomyces cerevisiae. The benchmark quantities precision and recall were used as performance measures. The results show that the proposed algorithm produced less false edges and significantly improved the precision, as compared to the existing algorithm. For further analysis the performance of the algorithms was observed over different sizes of data.
We have proposed a new algorithm that implements the PMDL principle for inferring gene regulatory networks from time series DNA microarray data that eliminates the need of a fine tuning parameter. The evaluation results obtained from both synthetic and actual biological data sets show that the PMDL principle is effective in determining the MI threshold and the developed algorithm improves precision of gene regulatory network inference. Based on the sensitivity analysis of all tested cases, an optimal CMI threshold value has been identified. Finally it was observed that the performance of the algorithms saturates at a certain threshold of data size.
BMC Systems Biology 01/2010; 4 Suppl 1:S7. · 3.15 Impact Factor
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ABSTRACT: Abstract Background A number of models and algorithms have been proposed in the past for gene regulatory network (GRN) inference; however, none of them address the effects of the size of time-series microarray expression data in terms of the number of time-points. In this paper, we study this problem by analyzing the behaviour of three algorithms based on information theory and dynamic Bayesian network (DBN) models. These algorithms were implemented on different sizes of data generated by synthetic networks. Experiments show that the inference accuracy of these algorithms reaches a saturation point after a specific data size brought about by a saturation in the pair-wise mutual information (MI) metric; hence there is a theoretical limit on the inference accuracy of information theory based schemes that depends on the number of time points of micro-array data used to infer GRNs. This illustrates the fact that MI might not be the best metric to use for GRN inference algorithms. To circumvent the limitations of the MI metric, we introduce a new method of computing time lags between any pair of genes and present the pair-wise time lagged Mutual Information (TLMI) and time lagged Conditional Mutual Information (TLCMI) metrics. Next we use these new metrics to propose novel GRN inference schemes which provides higher inference accuracy based on the precision and recall parameters. Results It was observed that beyond a certain number of time-points (i.e., a specific size) of micro-array data, the performance of the algorithms measured in terms of the recall-to-precision ratio saturated due to the saturation in the calculated pair-wise MI metric with increasing data size. The proposed algorithms were compared to existing approaches on four different biological networks. The resulting networks were evaluated based on the benchmark precision and recall metrics and the results favour our approach. Conclusions To alleviate the effects of data size on information theory based GRN inference algorithms, novel time lag based information theoretic approaches to infer gene regulatory networks have been proposed. The results show that the time lags of regulatory effects between any pair of genes play an important role in GRN inference schemes.
BMC Bioinformatics. 01/2010;
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ABSTRACT: Abstract
Background
Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold which defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we proposed a new inference algorithm which incorporated mutual information (MI), conditional mutual information (CMI) and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter.
Results
The performance of the proposed algorithm was evaluated using both synthetic time series data sets and a biological time series data set for the yeast Saccharomyces cerevisiae . The benchmark quantities precision and recall were used as performance measures. The results show that the proposed algorithm produced less false edges and significantly improved the precision, as compared to the existing algorithm. For further analysis the performance of the algorithms was observed over different sizes of data.
Conclusions
We have proposed a new algorithm that implements the PMDL principle for inferring gene regulatory networks from time series DNA microarray data that eliminates the need of a fine tuning parameter. The evaluation results obtained from both synthetic and actual biological data sets show that the PMDL principle is effective in determining the MI threshold and the developed algorithm improves precision of gene regulatory network inference. Based on the sensitivity analysis of all tested cases, an optimal CMI threshold value has been identified. Finally it was observed that the performance of the algorithms saturates at a certain threshold of data size.
BMC Systems Biology. 01/2010;
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International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing, IJCBS 2009, Shanghai, China, 3-5 August 2009; 01/2009