## Applying dynamic bayesian networks to perturbed gene expression data (2006)

Venue: | BMC bioinformatics |

Citations: | 11 - 0 self |

### BibTeX

@ARTICLE{Dojer06applyingdynamic,

author = {Norbert Dojer and Anna Gambin and Jerzy Tiuryn},

title = {Applying dynamic bayesian networks to perturbed gene expression data},

journal = {BMC bioinformatics},

year = {2006},

volume = {7},

pages = {249}

}

### OpenURL

### Abstract

Abstract Motivation: A central goal of molecular biology is to understand the regulatory mechanisms of gene transcription and protein synthesis. Because of their solid basis in statistics, allowing to deal with the stochastic aspects of gene expressions and noisy measurements in a natural way, Bayesian networks appear attractive in the field of inferring gene interactions structure from microarray experiments data. However, the basic formalism has some disadvantages, e.g. it is sometimes hard to distinguish between the origin and the object of an interaction. Two kinds of microarray experiments yield data particularly rich in information regarding the direction of interactions: time series and perturbation experiments. In order to correctly handle them, the basic formalism must be modified. For example, dynamic Bayesian networks apply to time series microarray data. Results: We extend the framework of dynamic Bayesian networks in order to handle perturbations. A new discretization method, specialized for datasets from time series perturbations experiments, is also introduced. We compare networks inferred from realistic simulations data by our method and by dynamic Bayesian networks learning techniques. We conclude that application of our method substantially improves inferring. 1 Introduction As most genetic regulatory systems involve many components connected through complex networks of interactions, formal methods and computer tools for modeling and simulating are needed. Therefore, various formalisms were proposed to describe genetic regulatory systems, including Boolean networks and their generalizations, ordinary and partial differential equations, stochastic equations and Bayesian networks (see [4] for a review). While differential and stochastic equations describe the biophysical processes at a very refined level of detail and prove useful in simulations of well studied systems, Bayesian networks appear attractive in the field of inferring the regulatory network structure from gene expression data. The reason is that their learning techniques have solid basis in statistics, allowing to deal with the stochastic aspects of gene expressions and noisy measurements in a natural way.

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Citation Context ...equently, one has to choose between restricting to small gene networks (a relatively quick algorithm was given in [13]) and inferring suboptimal networks by heuristic search methods (see for instance =-=[5]-=-). It should be also pointed out that the basic BN formalism has some major limitations. First, several networks with the same undirected graph structure but different directions of some edges may rep... |

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Citation Context ... protein and dimer X, respectively, finally X \DeltasY stands for a transcription factor bound to a promoter. The system is composed of structures reported in the biological literature (see [1], [2], =-=[7]-=-), i.e. a hysteretic oscillator, a genetic switch, cascades and a ligand binding mechanism that influences transcription (during the simulation, the ligand is injected for a short time). The whole net... |

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Citation Context ...relaxed. Given a set of time series of expression data, the learning techniques adapted from BNs allow one to infer dynamic networks that well match the temporal evolution recorded in the series (see =-=[6]-=-, [11], [14], [12], [15], [8], [9], [18]). A special treatment is required for experiments, in which expression of some genes were perturbed (e.g. knockout experiments). Since perturbations change the... |

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Citation Context ...ed. Given a set of time series of expression data, the learning techniques adapted from BNs allow one to infer dynamic networks that well match the temporal evolution recorded in the series (see [6], =-=[11]-=-, [14], [12], [15], [8], [9], [18]). A special treatment is required for experiments, in which expression of some genes were perturbed (e.g. knockout experiments). Since perturbations change the struc... |

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Citation Context ...series of expression data, the learning techniques adapted from BNs allow one to infer dynamic networks that well match the temporal evolution recorded in the series (see [6], [11], [14], [12], [15], =-=[8]-=-, [9], [18]). A special treatment is required for experiments, in which expression of some genes were perturbed (e.g. knockout experiments). Since perturbations change the structure of interactions (r... |

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Citation Context ...ns (regulation of affected genes is excluded), the learning techniques have to use data selectively. Inferring networks from perturbed expression profiles by means of BNs was investigated in [14] and =-=[16]-=-. In this report we extend the framework of DBN in order to handle perturbations and introduce a discretization method specialized for datasets from time series perturbations experiments. We compare n... |

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Citation Context ...er, as it was shown in [3], the problem of finding an optimal network is NP-hard. Consequently, one has to choose between restricting to small gene networks (a relatively quick algorithm was given in =-=[13]-=-) and inferring suboptimal networks by heuristic search methods (see for instance [5]). It should be also pointed out that the basic BN formalism has some major limitations. First, several networks wi... |

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Citation Context ...between the above two extremes is to apply the learning procedure to data generated by a system of ordinary differentional equations. In the present study we generate data using the model proposed in =-=[17]-=-. The model consists of 54 species of molecules, representing 10 genes with their transcription factors, promoters, mRNAs, proteins and protein dimers, connected through 97 elementary reactions, inclu... |

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Citation Context ...ter, mRNA, protein and dimer X, respectively, finally X \DeltasY stands for a transcription factor bound to a promoter. The system is composed of structures reported in the biological literature (see =-=[1]-=-, [2], [7]), i.e. a hysteretic oscillator, a genetic switch, cascades and a ligand binding mechanism that influences transcription (during the simulation, the ligand is injected for a short time). The... |