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Traditional biochemical research has resulted in a good understanding of many aspects of metabolism. However, this reductionist approach is time consuming and requires substantial resources, thus raising the question whether modern metabolomics and genomics should take over and replace the targeted experiments of old. We proffer that such a replacement is neither feasible not desirable and propose instead the tight integration of modern, system-wide omics with traditional experimental bench science and dedicated computational approaches. This integration is an important prerequisite toward the optimal acquisition of knowledge regarding metabolism and physiology in health and disease. The commentary describes advantages and drawbacks of current approaches to assessing metabolism and highlights the challenges to be overcome as we strive to achieve a deeper level of metabolic understanding in the future.

The three-legged stool of understanding metabolism: integrating metabolomics with biochemical genetics and computational modeling