Search for the gene modules and genetic networks of the yeast Saccharomyces cerevisiae

초록

Phenotypic diversity of eukaryotes arises from the versatile properties of the system established by assembling gene modules, constructing inter-modular networks, and selecting proper paths on the network against environmental conditions. Therefore, analysis of the gene modules is an essential step for understanding the relationship between genotypes and phenotypes. In this study, to identify gene modules of the yeast, we used gene expression data, measured by Spellman et al. To identify the specific activity of each gene module, the steady-state component represented by the 1st eigengene of gene expression data was removed by using the normalization method proposed by Alter et al. We clustered the yeast data and refined clusters by increasing the entropy. As the results of clustering, the 47 clusters were obtained from 3,744 genes. To identify the biological significance of each cluster, a statistical analysis of Gene Ontology term was performed, and we observed the relation between the biological function and the phase of each cluster. The clusters between 90 and 180 degrees in phase (Cluster 1,26,31,32) included many genes associated with the S phase, and `DNA replication` and `DNA repair` were found to be the major functions as a result of the Gene Ontology analysis; the clusters between 220 and 310 degrees in phase (Cluster 0,20,40,27) mostly consisted of the genes associated with the M phase and significantly had biological functions of `Cell division` and `Cell wall organization`; and the genes, related to `Cellular response to heat` and `Response to stress`, were concentrated on the clusters between 0 and 90 degrees in phase (Cluster 45,16,7). We defined a gene module as the cluster associated with one phenotype, inferred an inter-modular network, and searched for the maximum flow of information with the analysis about the relation between gene modules and the phenotypes. Also, gene-interaction-networks were inferred from gene interaction data of the Saccharomyces genome database for validation of the gene modules and the inter-modular network.