Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.
Environ Int. 2021 Nov;156:106630. doi: 10.1016/j.envint.2021.106630. Epub 2021 May 15.
The holistic characterisation of the human internal chemical exposome using high-resolution mass spectrometry (HRMS) would be a step forward to investigate the environmental ætiology 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.
使用高分辨率质谱（HRMS）对人类内部化学外显子组进行全面描述将是向前迈进的一步，可以以前所未有的精度研究慢性病的环境病因。基于 HRMS 的方法目前可用于在大量来自人类队列的生物样本中重复分析数千种内源性代谢物以及外源性化学物质及其生物转化产物。这些方法为发现与许多慢性疾病相关的未被识别的暴露标志物和代谢效应提供了坚实的基础。然而，仍然存在一些限制，需要加以克服，以便化学外显组学能够在流行病学研究中提供对影响疾病易感性的化学暴露的无偏检测。其中一些限制包括：（i）分析技术缺乏通用性，无法捕获广泛的化学物质多样性；（ii）分析灵敏度不足，无法检测从有限样本量中痕量（甚至超痕量）存在的外源性（和内源性）化学物质；（iii）注释/鉴定过程缺乏自动化。在本文中，我们讨论了一些技术和方法学限制，这些限制阻碍了基于 HRMS 的方法的应用，并提出了推动更全面地描述内部化学外显子组的初步步骤。我们还讨论了其他挑战，包括需要协调以及评估内部化学外显子动态性质固有困难，以及建立强大的国际合作、高级网络和可持续研究基础设施的必要性。还需要大量的研究、技术开发和创新的生物信息学工具来描述和表征内部化学外显子组的“无形”（未被描述）、“隐藏”（未被检测到）和“黑暗”（未被注释）成分，并且需要跨多个研究领域进行协调努力。
