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Stable isotope-labeling studies in metabolomics: new insights into structure and dynamics of metabolic networks

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The rapid emergence of metabolomics has enabled system-wide measurements of metabolites in various organisms. However, advances in the mechanistic understanding of metabolic networks remain limited, as most metabolomics studies cannot routinely provide accurate metabolite identification, absolute quantification and flux measurement. Stable isotope labeling offers opportunities to overcome these limitations. Here we describe some current approaches to stable isotope-labeled metabolomics and provide examples of the significant impact that these studies have had on our understanding of cellular metabolism. Furthermore, we discuss recently developed software solutions for the analysis of stable isotope-labeled metabolomics data and propose the bioinformatics solutions that will pave the way for the broader application and optimal interpretation of system-scale labeling studies in metabolomics.

Metabolomics is a rapidly growing field of postgenomic biology focusing on system-wide studies of metabolite levels and transformations in biological samples. Recent advances in mod­ern high-throughput bioanalytical platforms, in combination with rapidly improving compu­tational capabilities for data analysis and inter­pretation, and the free availability of numerous organism-specific metabolite databases, make it possible to annotate and quantify hundreds of metabolites in a single experiment. The resulting metabolite profiles provide a highly informative snapshot of an organism’s physiology and are widely used both in fundamental biology and in clinical research.

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