Historical Exposomics And High Resolution Mass Spectrometry

Awareness of the exposome and its influence on health has increased in the last decade. As past exposures can cause changes in human health many years later, delving into the past is relevant for both diagnostic and prevention purposes, but remains a challenging task. Lifestyle, diet and socioeconomic information of the past should be well documented and compatible with modern data science methods. While chemical analysis nowadays makes use of High Resolution Mass Spectrometry (HR-MS) for highly sensitive and comprehensive coverage of samples plus retrospective analysis, these data archives are in the very early stages. Since past measurements are often only available for a limited set of chemicals, adding to this knowledge requires careful selection of sample types and sampling sites, which may not always be available. The choice of analytes and analytical methods should be suitable for the study question—which is not always clear in advance in exposomics. Data interpretation and the use of appropriate databases are indispensable for a proper exposure assessment, and as databases and knowledge grow, re-analysis of physically or digitally archived samples could enable “continuous monitoring” efforts. This review focusses on the chemical analytical approaches necessary to capture the complexity of the historical exposome. Various sample types, analytes as well as analyses and data interpretation methods are discussed in relation to chemical exposures, while the connection to health remains in focus. It ends with perspectives and challenges in assessing the historical exposome, discussing how we can “learn from the past” to build a better future.

FAIR-ifying the Exposome Journal: Templates for Chemical Structures and Transformations

The exposome, the totality of lifetime exposures, is a new and highly complex paradigm for health and disease. Tackling this challenge requires an effort well beyond single individuals or laboratories, where every piece of the puzzle will be vital. The launch of this new Exposome journal coincides with the evolution of the exposome through its teenage years and into a growing maturity in an increasingly open and FAIR (findable, accessible, interoperable, reusable) world. This letter discusses how both authors and the Exposome journal alike can help increase the FAIRness of the chemical structural information and the associated metadata in the journal, aiming to capture more details about the chemistry of exposomics. The proposed chemical structure template can serve as an interoperable supplementary format that is made accessible through the website and more findable by linking the DOI of this data file to the article DOI metadata, supporting further reuse. An additional Transformations template provides authors with a means to connect predecessor (parent, substrate) molecules to successor (transformation product, metabolite) molecules and thus provide FAIR connections between observed (i.e., experimental) chemical exposures and biological responses, to help improve the public knowledgebase on exposome-related transformations. These connections are vital to extend current biochemical knowledge and to fulfil the current Exposome definition of “the cumulative measure of environmental influences and associated biological responses throughout the lifespan including exposures from the environment, diet, behaviour, and endogenous processes”.

Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction

Chemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health. Although environmental exposures typically include multiple chemicals, organismal studies on oxidative stress derived from chemical agents commonly study exposures to individual compounds. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions in the nematode C. elegans, by quantitatively assessing levels of gst-4 expression. Our results indicate that naphthoquinone mixtures drive responses differently than individual components, and that altering environmental conditions, such as increased heat and reduced food availability, result in dramatically different oxidative stress responses mounted by C. elegans. When exposed to heat, the oxidative stress response is diminished. Notably, when exposed to limited food, the oxidative stress response specific to juglone is significantly heightened, while identified antagonistic interactions between some naphthoquinone components in mixtures are abolished. This implies that organismal responses to xenobiotics is confounded by environment and stressor interactions. Given the high number of variables under study, and their potential combinations, a simplex centroid design was used to capture such non-trivial response over the design space. This makes the case for the adoption of Design of Experiments approaches as they can greatly expand the experimental space probed in noisy biological readouts, and in combinatorial experiments. Our results also reveal gaps in our current knowledge of the organismal oxidative stress response, which can be addressed by employing sophisticated design of experiments approaches to identify significant interactions.

Plasma metabolomics of autism spectrum disorder and influence of shared components in proband families

Prevalence of autism spectrum disorder has been increasing in the U.S. in the past decades. The exact mechanisms remain enigmatic and diagnosis of the disease still relies primarily on assessment of behavior. Subjects were enrolled at the Boston Children’s Hospital in years 2007–2012. We first used a case-control design (75 idiopathic cases and 29 controls) to identify plasma biomarkers of autism spectrum disorder through a metabolome-wide association study approach. Then we leveraged a family-based design (31 families) to investigate the influence of shared genetic and environmental components on the autism-associated features. Using untargeted high-resolution mass spectrometry metabolomics platforms, we detected 19 184 features. 191 of them were associated with autism spectrum disorder (false discovery rate < 0.05). We putatively annotated 30 features that had an odds ratio between <0.01 to 5.84. An identified endogenous metabolite, O-phosphotyrosine, was associated with an extremely low autism odds (OR 0.17, 95% CI 0.06–0.39). We also found that glutathione metabolism was associated with autism spectrum disorder (p = 0.048). Correlations of the significant features between proband and parents were low (median = 0.09). Of the 30 annotated features, the median correlations within families (proband-parents) were -0.15 and 0.24 for the endogenous and exogenous metabolites respectively. We hypothesize that, without feature identification, family-based correlation analysis of autism-associated features can be an alternative way to assist the prioritization of potentially diagnostic features. A panel of autism spectrum disorder diagnostic metabolic markers with high specificity could be derived upon further studies.

Analytical strategies for chemical exposomics: exploring limits and feasibility

Tackling the challenges of chemical exposomics will require the implementation of diverse analytical strategies and technological advancements. Herein, high-resolution mass spectrometry-based methods applied in current chemical exposome studies have been surveyed and are shown to be limited. Notably, liquid chromatography separations almost exclusively employ reversed-phase C18 columns using water-methanol gradients with formic acid additive, whilst gas chromatography is underexploited in the field at this stage. A systematic evaluation of strategies applied in related disciplines (i.e. metabolomics, proteomics, multi-residue trace analysis) was undertaken to provide practical guidance for the development of chemical exposomics. The approaches were assessed on the basis of their costs (i.e. capital expenditure, overhead and maintenance fees, expertise required, consumables) and potential benefits (i.e. improvements to sensitivity, coverage, reproducibility, throughput, ease of use) to prioritize those with promise for chemical exposomics application. Alongside a need for technological investments (e.g. advanced hardware updates), numerous low cost strategies showed high potential benefits (e.g. different column phases, enhanced sample fractionation) and are feasible for rapid adoption.