Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The “exposome” concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resolution mass spectrometry and network science have allowed us to take the first steps toward a comprehensive assessment of the exposome. Given the increased recognition of the dominant role that nongenetic factors play in disease, an effort to characterize the exposome at a scale comparable to that of the human genome is warranted.

Empirical spatial air pollution models have been applied extensively to assess exposure in epidemiological studies with increasingly sophisticated and complex statistical algorithms beyond ordinary linear regression. However, different algorithms have rarely been compared in terms of their predictive ability. This study compared 16 algorithms to predict annual average fine particle (PM2.5) and nitrogen dioxide (NO2) concentrations across Europe. The evaluated algorithms included linear stepwise regression, regularization techniques and machine learning methods. Air pollution models were developed based on the 2010 routine monitoring data from the AIRBASE dataset maintained by the European Environmental Agency (543 sites for PM2.5 and 2399 sites for NO2), using satellite observations, dispersion model estimates and land use variables as predictors. We compared the models by performing five-fold cross-validation (CV) and by external validation (EV) using annual average concentrations measured at 416 (PM2.5) and 1396 sites (NO2) from the ESCAPE study. We further assessed the correlations between predictions by each pair of algorithms at the ESCAPE sites. For PM2.5, the models performed similarly across algorithms with a mean CV R2 of 0.59 and a mean EV R2 of 0.53. Generalized boosted machine, random forest and bagging performed best (CV R2~0.63; EV R2 0.58-0.61), while backward stepwise linear regression, support vector regression and artificial neural network performed less well (CV R2 0.48-0.57; EV R2 0.39-0.46). Most of the PM2.5 model predictions at ESCAPE sites were highly correlated (R2 > 0.85, with the exception of predictions from the artificial neural network). For NO2, the models performed even more similarly across different algorithms, with CV R2s ranging from 0.57 to 0.62, and EV R2s ranging from 0.49 to 0.51. The predicted concentrations from all algorithms at ESCAPE sites were highly correlated (R2 > 0.9). For both pollutants, biases were low for all models except the artificial neural network. Dispersion model estimates and satellite observations were two of the most important predictors for PM2.5 models whilst dispersion model estimates and traffic variables were most important for NO2 models in all algorithms that allow assessment of the importance of variables. Different statistical algorithms performed similarly when modelling spatial variation in annual average air pollution concentrations using a large number of training sites.

Derived from the term exposure, the exposome is an omic-scale characterization of the nongenetic drivers of health and disease. With the genome, it defines the phenome of an individual. The measurement of complex environmental factors that exert pressure on our health has not kept pace with genomics and historically has not provided a similar level of resolution. Emerging technologies make it possible to obtain detailed information on drugs, toxicants, pollutants, nutrients, and physical and psychological stressors on an omic scale. These forces can also be assessed at systems and network levels, providing a framework for advances in pharmacology and toxicology. The exposome paradigm can improve the analysis of drug interactions and detection of adverse effects of drugs and toxicants and provide data on biological responses to exposures. The comprehensive model can provide data at the individual level for precision medicine, group level for clinical trials, and population level for public health.

Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences. Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences.

Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).