Quantitative metabolomics: a phantom?

• Quantitative metabolomics is a crucial ingredient for systems biology of microorganism.
• Measurement protocols for intracellular metabolite quantification are highly complex and error-prone.
• Thorough analyses of systematic and random errors are essential to increase both, accuracy and precision, of in vivo measurement data.
• At current state of the art many sources of systematic errors are known and can be corrected.
• However, establishing a gold standard fails due to fundamental limitations.

‘Mass specs are precise but biology is not!’ is a frequently heard argument when quantitative experimental data do not fit into the overall picture. The problem with this opinion is that the significance of measured biological data becomes a matter of gut feeling. Doubtlessly, the measurement precision of modern mass spectrometers is far better than the reproducibility of biological experiments. However, precisely for this reason, technical reproduction of mass spectrometric measurements neither characterizes the whole experiment from cell cultivation to producing biological data nor says anything about systematic errors in the overall measurement procedure. Taking quantitative metabolomics as a fruitful example, we deal with the question of why it is so difficult to say something precise about imprecision in biology.