Relating transcription factors, modules of genes and cultivation conditions in Saccharomyces cerevisiae

Usually, the functionality of a module of co-expressed genes is derived from enrichment within the module of a particular gene annotation category. The systematic setup of the chemostat cultivation experiments employed in this study, where Saccharomyces cerevisiae was grown under four different nutrient limitations, both aerobically and anaerobically. allows us to define the functionality of a module in terms of the module regulation pattern as a function of the growth parameters. In addition, we assign particular transcription factors (TF's) to each module, thus establishing a direct link between transcription factors and growth conditions. To define a module, the expression data is first discretized employing Lloyd quantization. This process assigns, for each differentially expressed gene in each of the growth conditions, one of three values: upregulated, down-regulated or common level. A module is then defined as a group of genes with identical discretized expression patterns across all the growth conditions. To link a module to particular TF's, we exploit a recently published high quality dataset, which lists, for each gene which TF's can bind the upstream region of that gene, and thereby manipulate its expression. This enabled us to employ the hypergeometric distribution to establish statistically significant enrichment of TF's in particular modules. Such a link suggests a role for the TF in the regulation of the genes in the module. In addition to many known relationships, various putative relationships were predicted. These include the regulatory role of Tye7p in sulfur-limited growth.