The work presented here is a first step toward a long term goal of systems biology, the complete elucidation of the gene regulatory networks of a living organism. To this end, we have employed DNA microarray technology to identify genes involved in the regulatory networks that facilitate the transition of Escherichia coli cells from an aerobic to an anaerobic growth state. We also report the identification of a subset of these genes that are regulated by a global regulatory protein for anaerobic metabolism, FNR. Analysis of these data demonstrated that the expression of over one-third of the genes expressed during growth under aerobic conditions are altered when E. coli cells transition to an anaerobic growth state, and that the expression of 712 (49%) of these genes are either directly or indirectly modulated by FNR. The results presented here also suggest interactions between the FNR and the leucine-responsive regulatory protein (Lrp) regulatory networks. Because computational methods to analyze and interpret high dimensional DNA microarray data are still at an early stage, and because basic issues of data analysis are still being sorted out, much of the emphasis of this work is directed toward the development of methods to identify differentially expressed genes with a high level of confidence. In particular, we describe an approach for identifying gene expression patterns (clusters) obtained from multiple perturbation experiments based on a subset of genes that exhibit high probability for differential expression values.The enteric bacterium Escherichia coli, like many commensal and pathogenic microorganisms, thrives in the gastrointestinal tract of humans and other warm-blooded animals. In this environment, oxygen required for respiration and energy generation is in limited supply. Thus, the cell must derive energy from anaerobic respiration with alternative electron acceptors such as nitrate and fumarate or by fermentation of simple sugars. Metabolic transitions between aerobic and anaerobic growth states occur when E. coli cells enter an animal host and colonize the gastrointestinal tract, and when individual cells reposition themselves in new microenvironments inside the host. Each of these transitions is accompanied by fluctuations in oxygen tension. The cell responds to these fluctuations by modulating its central metabolic pathways for carbon and energy flow