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Letter

Control of Yeast Filamentous-Form Growth by Modules in an Integrated Molecular Network

¹ Institute for Systems Biology, Seattle, Washington 98103, USA ² University of Washington, Departments of Management Science, Finance, and Statistics, Seattle, Washington 98195, USA

On solid growth media with limiting nitrogen source, diploid budding-yeast cells differentiate from the yeast form to a filamentous, adhesive, and invasive form. Genomic profiles of mRNA levels in Saccharomyces cerevisiae yeast-form and filamentous-form cells were compared. Disparate data types, including genes implicated by expression change, filamentation genes known previously through a phenotype, protein–protein interaction data, and protein–metabolite interaction data were integrated as the nodes and edges of a filamentation-network graph. Application of a network-clustering method revealed 47 clusters in the data. The correspondence of the clusters to modules is supported by significant coordinated expression change among cluster co-member genes, and the quantitative identification of collective functions controlling cell properties. The modular abstraction of the filamentation network enables the association of filamentous-form cell properties with the activation or repression of specific biological processes, and suggests hypotheses. A module-derived hypothesis was tested. It was found that the 26S proteasome regulates filamentous-form growth.

³ Corresponding author.
E-MAIL tgalitski{at}systemsbiology.org; FAX (206) 732-1299.

[Supplemental material is available online at www.genome.org. Software is available at http://labs.systemsbiology.net/galitski. The gene expression data from this study have been submitted to Gene Expression Omnibus database under accession no. GSE679.]

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