在现代“经济学”时代,人类暴露组的测量是遗传驱动因素和疾病结果之间的关键缺失环节。高分辨率质谱(HRMS),常规用于蛋白质组学和代谢组学,已成为广泛分布化学暴露剂和相关生物分子以进行准确质量测量的领先技术,高灵敏度,快速数据采集,增加化学空间的分辨率。非目标方法越来越容易获得,支持从传统假设驱动的转变,以定量为中心的有针对性的分析,以数据驱动,产生假设的化学暴露广泛的分析。然而,基于HRMS的曝光组学遇到了独特的挑战。需要新的分析和计算基础设施,以通过简化、可扩展,协调的工作流程和数据管道,允许纵向化学品暴露组跟踪,回顾性验证,和多组学整合,以实现有意义的健康导向推断。在这篇文章中,我们调查了关于最先进的基于HRMS的技术的文献,回顾当前的分析工作流程和信息管道,并为化学家提供有关暴露组学方法的最新参考,毒理学家,流行病学家,护理提供者,以及健康科学和医学的利益相关者。我们建议努力对适合用途的平台进行基准测试,以扩大化学空间的覆盖范围,包括气/液色谱-HRMS(GC-HRMS和LC-HRMS),讨论机会,挑战,以及推进新兴领域的战略。
In the modern \"omics\" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.