Perspective Special Focus Issue: Methods & Techniques for Metabolic Phenotyping


Integrating ion mobility spectrometry into mass spectrometry-based exposome measurements: what can it add and how far can it go?


Measuring the exposome remains a challenge due to the range and number of anthropogenic molecules that are encountered in our daily lives, as well as the complex systemic responses to these exposures. One option for improving the coverage, dynamic range and throughput of measurements is to incorporate ion mobility spectrometry (IMS) into current MS-based analytical methods. The implementation of IMS in exposomics studies will lead to more frequent observations of previously undetected chemicals and metabolites. LC-IMS-MS will provide increased overall measurement dynamic range, resulting in detections of lower abundance molecules. Alternatively,


the throughput of IMS-MS alone will provide the opportunity to


analyze many thousands of longitudinal samples over lifetimes of exposure, capturing evidence of transitory accumulations of chemicals or metabolites. The volume of data corresponding to these new chemical observations will almost certainly outpace the generation of reference data to enable their confident identification. In this perspective, we briefly review the state-of-the-art in measuring the exposome, and discuss the potential use for IMS-MS and the physico-chemical property of collisional cross section in both exposure assessment and molecular identification.


First draft submitted: 16 September 2016; Accepted for publication: 12 October 2016; Published online: 6 December 2016


Keywords: collision cross section • exposome • ion mobility spectrometry • mass spectrom- etry • metabolome


The majority of human disease (>90%) is attributable to a combination of individual genetic factors and nongenetic ‘environmen- tal factors’ [1–3]. The former can be read- ily assessed using rapid genome sequenc- ing technologies, whereas the latter can be assessed or estimated using a variety of ana- lytical methods [3,4]. To represent these non- genetic environmental factors, the concept of the ‘exposome’ was defined by Christopher Wild as the sum of all exposures over a life- time to chemical, social and biological agents that influence human health [1]. The expo- some was proposed as the natural comple- ment to the genome, with the recognition that the phenome (sum of individual traits) was a product of both the genome and an


10.4155/bio-2016-0244 © 2017 Battelle Memorial Institute


e xposome – the environment within which genes are expressed. The exposome embraces the totality of


both external and internal exposure. Exter- nal exposure is mainly to chemicals in the air, water, soil, diet or consumer products, and internal exposures correlate to molecu- lar changes within body compartments. Furthermore,


be to products of normal metabolism or in response


to external


these internal exposures can exposures,


including


chemical, infectious or social [5]. External exposure measurements are often more con- venient and cost effective, particularly when the goal is to identify sources of exposure. Internal exposures are often preferred when the objective is to identify exposure–disease


Bioanalysis (2017) 9(1), 81–98 ISSN 1757-6180 Thomas O Metz*,1 , Erin S


Baker1, Emma L Schymanski2 Ryan S Renslow1, Dennis G Thomas1


, Tim J Causon3


Teeguarden1,4 1


WA, USA 2


K Webb1, Stephan Hann3 Richard D Smith1


, Ian ,


& Justin G Biological Sciences Division, Pacific Northwest National Laboratory, Richland,


Eawag, Swiss Federal Institute of Aquatic Science & Technology,


Dübendorf, Switzerland 3


Division of Analytical Chemistry,


Department of Chemistry, University of Natural Resources & Life Sciences (BOKU


Vienna), Vienna, Austria 4


Department of Environmental &


Molecular Toxicology, Oregon State University, Corvallis, OR, USA *Author for correspondence: thomas.metz@pnnl.gov


,


part of


28


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