Bayesian Inference of Gene Regulatory Networks Using Gene Expression Time Series Data
Differential equations have been established to model the dynamic behavior of gene regulatory networks in the last few years. They provide a detailed insight into regulatory processes at a molecular level. However, in a top down approach aiming at the inference of the underlying regulatory network from gene expression data, the corresponding optimization problem is usually severely underdetermined, since the number of unknowns far exceeds the number of timepoints available. Thus one has to restrict the search space in a biologically meaningful way.
We use differential equations to model gene regulatory networks and introduce a Bayesian regularized inference method that is particularly suited to deal with sparse and noisy datasets. Network inference is carried out by embedding our model into a probabilistic framework and maximizing the posterior probability. A specifically designed hierarchical prior distribution over interaction strenghts favours sparse networks, enabling the method to efficiently deal with small datasets.
Results on a simulated dataset show that our method correctly learns network structure and model parameters even for short time series. Furthermore, we are able to learn main regulatory interactions in the yeast cell cycle.
Keywordsgene regulatory network ordinary differential equations network inference Bayesian regularization Saccharomyces cerevisiae cell cycle
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