Experiment-originated variations, and multi-peak and multi-origination phenomena in derivatization-based GC-MS metabolomics

Gas chromatography combined with mass spectrometry (GC-MS), in particular derivatization-based GC-MS, is one of the most commonly used analytical methods in metabolomics. However, experiment-derived variations and originations of chromatographic peaks are two fundamental issues that could influence interpretation of metabolic pathways. Here, we focus on some pitfalls and limitations, especially the commonly ignored multi-origination and multi-peak phenomena in derivatization-based GC-MS metabolomics. We use examples to illustrate that ignoring these two factors could lead to wrong interpretations of results and serious metabolic implications. We also discuss strategies to overcome some of these confounding factors.