Cheminformatics in MS-based environmental exposomics: Current achievements and future directions

Ljoncheva, Milka; Stepišnik, Tomaž; Džeroski, Sašo; Kosjek, Tina

doi:10.1016/j.teac.2020.e00099

Cited by 21 publications

(29 citation statements)

References 89 publications

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“…These approaches do generally work, however, for specific types of compounds, such as lipids. Several approaches using various indirect structure elucidation approaches as well as in silico spectral prediction approaches have been developed [ 53 , 54 , 55 , 56 , 57 ]. In untargeted analyses, it is possible to utilize the unique mass spectral features of, e.g., halogenated compounds, so that it is possible to screen these compounds based on the mass spectrum.…”

Section: Analytical Methodologiesmentioning

confidence: 99%

Metabolic Signatures of the Exposome—Quantifying the Impact of Exposure to Environmental Chemicals on Human Health

et al. 2020

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Human health and well-being are intricately linked to environmental quality. Environmental exposures can have lifelong consequences. In particular, exposures during the vulnerable fetal or early development period can affect structure, physiology and metabolism, causing potential adverse, often permanent, health effects at any point in life. External exposures, such as the “chemical exposome” (exposures to environmental chemicals), affect the host’s metabolism and immune system, which, in turn, mediate the risk of various diseases. Linking such exposures to adverse outcomes, via intermediate phenotypes such as the metabolome, is one of the central themes of exposome research. Much progress has been made in this line of research, including addressing some key challenges such as analytical coverage of the exposome and metabolome, as well as the integration of heterogeneous, multi-omics data. There is strong evidence that chemical exposures have a marked impact on the metabolome, associating with specific disease risks. Herein, we review recent progress in the field of exposome research as related to human health as well as selected metabolic and autoimmune diseases, with specific emphasis on the impacts of chemical exposures on the host metabolome.

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Section: Analytical Methodologiesmentioning

confidence: 99%

Metabolic Signatures of the Exposome—Quantifying the Impact of Exposure to Environmental Chemicals on Human Health

et al. 2020

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“…Despite many advances, chemical identification is still generally considered a bottleneck in many research fields (see e.g. [ 1 , 2 ]). Interest in the exposome [ 3 ] and the related exposomics field has increased as awareness of the influence of the external environment on health and disease has increased [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Empowering large chemical knowledge bases for exposomics: PubChemLite meets MetFrag

et al. 2021

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Compound (or chemical) databases are an invaluable resource for many scientific disciplines. Exposomics researchers need to find and identify relevant chemicals that cover the entirety of potential (chemical and other) exposures over entire lifetimes. This daunting task, with over 100 million chemicals in the largest chemical databases, coupled with broadly acknowledged knowledge gaps in these resources, leaves researchers faced with too much—yet not enough—information at the same time to perform comprehensive exposomics research. Furthermore, the improvements in analytical technologies and computational mass spectrometry workflows coupled with the rapid growth in databases and increasing demand for high throughput “big data” services from the research community present significant challenges for both data hosts and workflow developers. This article explores how to reduce candidate search spaces in non-target small molecule identification workflows, while increasing content usability in the context of environmental and exposomics analyses, so as to profit from the increasing size and information content of large compound databases, while increasing efficiency at the same time. In this article, these methods are explored using PubChem, the NORMAN Network Suspect List Exchange and the in silico fragmentation approach MetFrag. A subset of the PubChem database relevant for exposomics, PubChemLite, is presented as a database resource that can be (and has been) integrated into current workflows for high resolution mass spectrometry. Benchmarking datasets from earlier publications are used to show how experimental knowledge and existing datasets can be used to detect and fill gaps in compound databases to progressively improve large resources such as PubChem, and topic-specific subsets such as PubChemLite. PubChemLite is a living collection, updating as annotation content in PubChem is updated, and exported to allow direct integration into existing workflows such as MetFrag. The source code and files necessary to recreate or adjust this are jointly hosted between the research parties (see data availability statement). This effort shows that enhancing the FAIRness (Findability, Accessibility, Interoperability and Reusability) of open resources can mutually enhance several resources for whole community benefit. The authors explicitly welcome additional community input on ideas for future developments.

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“…However, challenges for regulators to perform NTA persist, particularly with respect to high-throughput data analysis and identification following the mass prioritisation and peak-picking steps described above. For example, regulators may lack specific NTA expertise and/or resources to apply the potentially many and complicated computational workflows [15,33] available for analysing the copious amounts of data. In addition to the time-consuming and complex nature of data interpretation, issues related to standardisation and reproducibility exist, as there is currently no 'one size fits all' approach to identifying compounds using NTA [16].…”

Section: Introductionmentioning

confidence: 99%

Retrospective non-target analysis to support regulatory water monitoring: from masses of interest to recommendations via in silico workflows

Lai

Singh

Kovalova³

et al. 2021

Environ Sci Eur

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Background Applying non-target analysis (NTA) in regulatory environmental monitoring remains challenging—instead of having exploratory questions, regulators usually already have specific questions related to environmental protection aims. Additionally, data analysis can seem overwhelming because of the large data volumes and many steps required. This work aimed to establish an open in silico workflow to identify environmental chemical unknowns via retrospective NTA within the scope of a pre-existing Swiss environmental monitoring campaign focusing on industrial chemicals. The research question addressed immediate regulatory priorities: identify pollutants with industrial point sources occurring at the highest intensities over two time points. Samples from 22 wastewater treatment plants obtained in 2018 and measured using liquid chromatography–high resolution mass spectrometry were retrospectively analysed by (i) performing peak-picking to identify masses of interest; (ii) prescreening and quality-controlling spectra, and (iii) tentatively identifying priority “known unknown” pollutants by leveraging environmentally relevant chemical information provided by Swiss, Swedish, EU-wide, and American regulators. This regulator-supplied information was incorporated into MetFrag, an in silico identification tool replete with “post-relaunch” features used here. This study’s unique regulatory context posed challenges in data quality and volume that were directly addressed with the prescreening, quality control, and identification workflow developed. Results One confirmed and 21 tentative identifications were achieved, suggesting the presence of compounds as diverse as manufacturing reagents, adhesives, pesticides, and pharmaceuticals in the samples. More importantly, an in-depth interpretation of the results in the context of environmental regulation and actionable next steps are discussed. The prescreening and quality control workflow is openly accessible within the R package Shinyscreen, and adaptable to any (retrospective) analysis requiring automated quality control of mass spectra and non-target identification, with potential applications in environmental and metabolomics analyses. Conclusions NTA in regulatory monitoring is critical for environmental protection, but bottlenecks in data analysis and results interpretation remain. The prescreening and quality control workflow, and interpretation work performed here are crucial steps towards scaling up NTA for environmental monitoring.

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Cheminformatics in MS-based environmental exposomics: Current achievements and future directions

Cited by 21 publications

References 89 publications

Metabolic Signatures of the Exposome—Quantifying the Impact of Exposure to Environmental Chemicals on Human Health

Metabolic Signatures of the Exposome—Quantifying the Impact of Exposure to Environmental Chemicals on Human Health

Empowering large chemical knowledge bases for exposomics: PubChemLite meets MetFrag

Retrospective non-target analysis to support regulatory water monitoring: from masses of interest to recommendations via in silico workflows

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