MSEA: metabolite set enrichment analysis in the MeltDB metabolomics software platform: metabolic profiling of Corynebacterium glutamicum as an example
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Gene set enrichment analysis (GSEA) has been successfully employed in transcriptomics and proteomics research for over 5 years. We have applied a modified GSEA approach to metabolomics, called metabolite set enrichment analysis (MSEA), and have integrated this method into the MeltDB platform. With the novel integrated functionality, we evaluate the applicability of the approach for metabolomics research by analyzing the metabolic profiles of industrial amino acid producer strains of Corynebacterium glutamicum. Metabolite sets are obtained from metabolic pathways defined in the KEGG and the newly created CglCyc databases. In the first experiment using MSEA, the metabolic profiling analyses compared glucose- and acetate-grown strains, and, in the second, a production strain series in which the carbon flow is shifted step-wise from the lysine pathway to the branching threonine, isoleucine, and methionine pathways. By identifying changes of the metabolic profile MSEA was able to identify the metabolic pathways activated while utilizing different carbon sources or those that have been genetically modified. The presented experimental results are publicly available at http://meltdb.cebitec.uni-bielefeld.de.
KeywordsMetabolite set enrichment analysis Corynebacterium glutamicum
HN and LJS acknowledge the financial support of the SysLogics Project (BMBF 0315275A) and MP that of the SysMAP Project (BMBF 0313704). NK acknowledges the support by a fellowship from the CLIB-Graduate Cluster Industrial Biotechnology. The authors wish to thank the BRF team for expert technical support. Furthermore, the authors thank Daniel Stephen Brooks (Department of Philosophy, University of Bielefeld, Germany) and John Quimby (Massachusetts Institute of Technology, Sinskey Laboratory, Cambridge, USA) for carefully reading the manuscript and helping with wording and phrasing.
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