We propose a new statistical method for constructing a genetic network from microarray gene expression data by using a Bayesian network. An essential point of Bayesian network construction is in the estimation of the conditional distribution of each random variable. We consider fitting nonparametric regression models with heterogeneous error variances to the microarray gene expression data to capture the nonlinear structures between genes. A problem still remains to be solved in selecting an optimal graph, which gives the best representation of the system among genes. We theoretically derive a new graph selection criterion from Bayes approach in general situations. The proposed method includes previous methods based on Bayesian networks. We demonstrate the effectiveness of the proposed method through the analysis of Saccharomyces cerevisiae gene expression data newly obtained by disrupting 100 genes. 1.

This thesis addresses the problems of modeling the gene regulatory system from multiple sources of large-scale datasets. In the first part, we develop a computational framework of building and validating simple, mechanistic models of gene regulation from multiple sources of data. These models, which we call physical network models, annotate the network of molecular interactions with several types of attributes (variables). We associate model attributes with physical interaction and knock-out gene expression data according to the confidence measures of data and the hypothesis that gene regulation is achieved via molecular interaction cascades. By applying standard model inference algorithms, we are able to obtain the configurations of model attributes which optimally fit the data. Because existing datasets do not provide sufficient constraints to the models, there are many optimal configurations which fit the data equally well. In the second part, we develop an information theoretic score to measure the expected capacity of new knock-out experiments in terms of reducing the model uncertainty. We collaborate with biologists to perform suggested knockout