Abstract

Background:

Recent developments in technologies have offered opportunities to measure the exposome with unprecedented accuracy and scale. However, because most investigations have targeted only a few exposures at a time, it is hypothesized that the majority of the environmental determinants of chronic diseases remain unknown.

Objectives:

We describe a functional exposome concept and explain how it can leverage existing bioassays and high-resolution mass spectrometry for exploratory study. We discuss how such an approach can address well-known barriers to interpret exposures and present a vision of next-generation exposomics.

Discussion:

The exposome is vast. Instead of trying to capture all exposures, we can reduce the complexity by measuring the functional exposome—the totality of the biologically active exposures relevant to disease development—through coupling biochemical receptor-binding assays with affinity purification–mass spectrometry. We claim the idea of capturing exposures with functional biomolecules opens new opportunities to solve critical problems in exposomics, including low-dose detection, unknown annotations, and complex mixtures of exposures. Although novel, biology-based measurement can make use of the existing data processing and bioinformatics pipelines. The functional exposome concept also complements conventional targeted and untargeted approaches for understanding exposure-disease relationships.

Conclusions:

Although measurement technology has advanced, critical technological, analytical, and inferential barriers impede the detection of many environmental exposures relevant to chronic-disease etiology. Through biology-driven exposomics, it is possible to simultaneously scale up discovery of these causal environmental factors. https://doi.org/10.1289/EHP8327

中文翻译：

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利用生物学驱动的方法绘制健康和疾病暴露组图：推动下一代环境发现的重要投资

摘要

背景：

技术的最新发展提供了以前所未有的精度和规模测量暴露组的机会。然而，由于大多数调查一次只针对少数暴露，因此假设慢性病的大多数环境决定因素仍然未知。

目标：

我们描述了功能性暴露组概念，并解释了它如何利用现有的生物测定和高分辨率质谱进行探索性研究。我们讨论这种方法如何解决解释暴露的众所周知的障碍，并提出下一代暴露组学的愿景。

讨论：

暴露量是巨大的。我们可以通过测量功能暴露组（与疾病发展相关的生物活性暴露的总体）来降低复杂性，而不是试图捕获所有暴露，通过将生化受体结合测定与亲和纯化质谱法相结合。我们声称，用功能生物分子捕获暴露的想法为解决暴露组学中的关键问题提供了新的机会，包括低剂量检测、未知注释和复杂的暴露混合物。虽然新颖，但基于生物学的测量可以利用现有的数据处理和生物信息学管道。功能性暴露组概念还补充了了解暴露与疾病关系的传统靶向和非靶向方法。

结论：

尽管测量技术很先进，但关键的技术、分析和推理障碍阻碍了与慢性病病因相关的许多环境暴露的检测。通过生物学驱动的暴露组学，可以同时扩大对这些因果环境因素的发现。https://doi.org/10.1289/EHP8327