@article{89439b0a110841c68c39ed17d3cd9637,
title = "Towards a comprehensive characterisation of the human internal chemical exposome: Challenges and perspectives",
abstract = "The holistic characterisation of the human internal chemical exposome using high-resolution mass spectrometry (HRMS) would be a step forward to investigate the environmental {\ae}tiology of chronic diseases with an unprecedented precision. HRMS-based methods are currently operational to reproducibly profile thousands of endogenous metabolites as well as externally-derived chemicals and their biotransformation products in a large number of biological samples from human cohorts. These approaches provide a solid ground for the discovery of unrecognised biomarkers of exposure and metabolic effects associated with many chronic diseases. Nevertheless, some limitations remain and have to be overcome so that chemical exposomics can provide unbiased detection of chemical exposures affecting disease susceptibility in epidemiological studies. Some of these limitations include (i) the lack of versatility of analytical techniques to capture the wide diversity of chemicals; (ii) the lack of analytical sensitivity that prevents the detection of exogenous (and endogenous) chemicals occurring at (ultra) trace levels from restricted sample amounts, and (iii) the lack of automation of the annotation/identification process. In this article, we discuss a number of technological and methodological limitations hindering applications of HRMS-based methods and propose initial steps to push towards a more comprehensive characterisation of the internal chemical exposome. We also discuss other challenges including the need for harmonisation and the difficulty inherent in assessing the dynamic nature of the internal chemical exposome, as well as the need for establishing a strong international collaboration, high level networking, and sustainable research infrastructure. A great amount of research, technological development and innovative bio-informatics tools are still needed to profile and characterise the “invisible” (not profiled), “hidden” (not detected) and “dark” (not annotated) components of the internal chemical exposome and concerted efforts across numerous research fields are paramount.",
keywords = "EWAS, Exposome, High-Resolution Mass Spectrometry, Internal chemical exposome, Non-targeted analysis, Suspect screening",
author = "Arthur David and Jade Chaker and Price, {Elliott J.} and Vincent Bessonneau and Chetwynd, {Andrew J.} and Vitale, {Chiara M.} and Jana Kl{\'a}nov{\'a} and Walker, {Douglas I.} and Antignac, {Jean Philippe} and Robert Barouki and Miller, {Gary W.}",
note = "Funding Information: This article was supported by the MoU signed between Inserm and the Mailman School of Public Health of Columbia University on Nov. 12 2019. JC was funded by the R{\'e}seau Doctoral en Sant{\'e} Publique. E.J.P. acknowledges support from the Czech Operational Programme Research, Development and Education – Project Postdoc@MUNI (No. CZ.02.2.69/ 0.0/0.0/16_027/0008360) and Czech Operational Programme Research, Development and Education – Project MSCAfellow4@MUNI (No. CZ.02.2.69/0.0/0.0/20_079/0017045). Funding Information: Several European (e.g., The Human Early-Life Exposome (HELIX) ( Vrijheid et al., 2014 ), EXPOsOMICS ( Vineis et al., 2017 )), and international (e.g., HERCULES ( Niedzwieck and Miller, 2019 ), NIH Human Health Exposure Analysis Resource (HHEAR) laboratory network) initiatives have already been deployed to perform large-scale exposomics studies ( Huhn et al., 2021 ) and develop research infrastructures aiming to expand analytical capabilities, to provide support for data analysis, and to train future researchers in exposomics. Recently, the European Human Exposome Network, a cluster of nine new Horizon 2020 Exposome projects representing 106 M€ funding from the EU over 5 years, has been launched to improve technologies and methodologies for exposome research and to better understand how environmental factors affect our health. All these collaborative projects involving large international partnerships have already provided and will keep providing very important landmarks for the successful implementation of chemical exposomics based on HRMS (as well as other technologies -e.g., sensors- or advanced statistical models to treat big data) in epidemiological studies. Funding Information: This article was supported by the MoU signed between Inserm and the Mailman School of Public Health of Columbia University on Nov. 12 2019. JC was funded by the R?seau Doctoral en Sant? Publique. E.J.P. acknowledges support from the Czech Operational Programme Research, Development and Education ? Project Postdoc@MUNI (No. CZ.02.2.69/ 0.0/0.0/16_027/0008360) and Czech Operational Programme Research, Development and Education ? Project MSCAfellow4@MUNI (No. CZ.02.2.69/0.0/0.0/20_079/0017045). Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = nov,
doi = "10.1016/j.envint.2021.106630",
language = "English",
volume = "156",
journal = "Environment international",
issn = "0160-4120",
publisher = "Elsevier Ltd.",
}