Metabolic Phenotyping by Liquid Chromatography ... - ACS Publications

Feb 19, 2015 - and biomarker discovery studies into biomarker validation and more widespread applications in human health and disease. However, as pra...
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Metabolic Phenotyping by Liquid Chromatography−Mass Spectrometry to Study Human Health and Disease he practice of “global metabolic profiling”, or metabolic phenotyping, of the type covered by the terms metabonomics/metabolomics has become an increasingly important area for many areas of biological science. For example, in the area of human health there has been a large amount of activity to seek and exploit novel biomarkers that reveal disease, indicate (or predict) response to therapy, and provide mechanistic understanding of underlying disease processes. This quest has resulted in the development and application of numerous advances in analytical science. To highlight some of these advances and applications in metabolic profiling this Virtual Issue has been assembled that contains a personal selection of ∼30 papers on metabolomics/metabonomics, published in the Journal of Proteome Research or Analytical Chemistry, covering the period 2011 to 2014. When tasked with putting this selection together, I foolishly assumed that it would be easy. In fact selecting only a fraction of the eligible manuscripts from the two journals was surprisingly (or perhaps not surprisingly!) hard. This difficulty was the result of the sheer range and quality of the choices available to me (you would be surprised just how may manuscripts turn up if you use the search criteria such as [metabolomics, metabonomics, 2011−2014, Analytical Chemistry, Journal of Proteome Research]. Narrowing down that choice to a manageable number required the development of some fairly brutal selection criteria. So, in the end I chose to go with my current analytical love affair which is developments in, and the application of, liquid chromatography hyphenated to mass spectrometry (especially where this involves the use of ultra (high) performance methods (U(H)PLC)). (There were also a number of less obvious selection criteria, such as not selecting any work which I have been directly involved in, and I apologize to my already much put upon coauthors for ensuring that their manuscripts are excluded from this collection because of their association with me!). In the case of the applications I have also chosen to limit this selection, as far as possible, to studies in humans, thus excluding all of those in plants, micro-organisms, and animals. As well as this I have attempted to balance my choices as evenly as possible between both journals, and while I include one or two papers from 2011, the selections are biased toward more recent publications. This is not to suggest that the value of the earlier publications is somehow lower than the more recent ones but, rather, reflects the current pace of innovation in this area. By focusing on LC−MS methods I have obviously missed the opportunity to include all of the many fine studies that have employed other information rich analytical technologies such as nuclear magnetic resonance (NMR) spectroscopy, gas chromatography (GC)−MS, and capillary electrophoresis (CE)−MS. This was not easy, but it was very educational, and I continue to be amazed at the breadth and quality of the work being published in this field. It is very clear to me that we have more than achieved critical analytical mass in this particular “omic” and are moving rapidly from proof of concept

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© 2015 American Chemical Society

and biomarker discovery studies into biomarker validation and more widespread applications in human health and disease. However, as practicing metabolomics/metabonomics experts know, there are considerable technical challenges that remain to be solved in metabolic profiling using LC−MS-based (and other) methods. Clearly the quality of the analytical chemistry is vital to success in this type of enterprise, but critical appraisal of the results, combined with anchoring the detected “biomarkers” within a plausible biological framework, are vital. This is important because many of the things that change in response to, for example, a disease are not specific to a particular condition but represent a general response to being unwell! No amount of analytical expertise and statistical brilliance can compensate for not thinking... So, Dear Reader, I hope that you enjoy my chosen papers for the excellent work they contain, accept the constraints that I placed on their selection, and forgive my omissions. Even with all of its imperfections I would hope that you too will enjoy the work that I have selected for your delight and edification. And, if I have whetted your appetite for a deeper dive into the literature, please be assured that both Analytical Chemistry and Journal of Proteome Research contain much more high-quality research in this area for you to discover. I have barely scratched the surface.

Ian D. Wilson, Chair



Drug Metabolism and Molecular Toxicology, Imperial College, London, U.K.

AUTHOR INFORMATION

Notes

Views expressed in this editorial are those of the author and not necessarily the views of the ACS.

Published: February 19, 2015 2519

DOI: 10.1021/acs.analchem.5b00409 Anal. Chem. 2015, 87, 2519−2519