Transcriptional Coordination of the Metabolic Network in Arabidopsis

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Abstract
Patterns of coexpression can reveal networks of functionally related genes and provide deeper understanding of processes requiring multiple gene products. We performed an analysis of coexpression networks for 1,330 genes from the AraCyc database of metabolic pathways in Arabidopsis (Arabidopsis thaliana). We found that genes associated with the same metabolic pathway are, on average, more highly coexpressed than genes from different pathways. Positively coexpressed genes within the same pathway tend to cluster close together in the pathway structure, while negatively correlated genes typically occupy more distant positions. The distribution of coexpression links per gene is highly skewed, with a small but significant number of genes having numerous coexpression partners but most having fewer than 10. Genes with multiple connections (hubs) tend to be single-copy genes, while genes with multiple paralogs are coexpressed with fewer genes, on average, than single-copy genes, suggesting that the network expands through gene duplication, followed by weakening of coexpression links involving duplicate nodes. Using a network-analysis algorithm based on coexpression with multiple pathway members (pathway-level coexpression), we identified and prioritized novel candidate pathway members, regulators, and cross pathway transcriptional control points for over 140 metabolic pathways. To facilitate exploration and analysis of the results, we provide a Web site (http://www.transvar.org/at_coexpress/analysis/web) listing analyzed pathways with links to regression and pathway-level coexpression results. These methods and results will aid in the prioritization of candidates for genetic analysis of metabolism in plants and contribute to the improvement of functional annotation of the Arabidopsis genome.