文章基本信息

标题：An annotation database for chemicals of emerging concern in exposome research
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作者：Jeroen Meijer ; Marja Lamoree ; Timo Hamers 等
期刊名称：Environment International
印刷版ISSN：0160-4120
电子版ISSN：1873-6750
出版年度：2021
卷号：152
页码：106511
DOI：10.1016/j.envint.2021.106511
出版社：Pergamon
摘要：Background Chemicals of Emerging Concern (CECs) include a very wide group of chemicals that are suspected to be responsible for adverse effects on health, but for which very limited information is available. Chromatographic techniques coupled with high-resolution mass spectrometry (HRMS) can be used for non-targeted screening and detection of CECs, by using comprehensive annotation databases. Establishing a database focused on the annotation of CECs in human samples will provide new insight into the distribution and extent of exposures to a wide range of CECs in humans. Objectives This study describes an approach for the aggregation and curation of an annotation database (CECscreen) for the identification of CECs in human biological samples. Methods The approach consists of three main parts. First, CECs compound lists from various sources were aggregated and duplications and inorganic compounds were removed. Subsequently, the list was curated by standardization of structures to create “MS-ready” and “QSAR-ready” SMILES, as well as calculation of exact masses (monoisotopic and adducts) and molecular formulas. The second step included the simulation of Phase I metabolites. The third and final step included the calculation of QSAR predictions related to physicochemical properties, environmental fate, toxicity and Absorption, Distribution, Metabolism, Excretion (ADME) processes and the retrieval of information from the US EPA CompTox Chemicals Dashboard. Results All CECscreen database and property files are publicly available (DOI: https://doi.org/10.5281/zenodo.3956586 ). In total, 145,284 entries were aggregated from various CECs data sources. After elimination of duplicates and curation, the pipeline produced 70,397 unique “MS-ready” structures and 66,071 unique QSAR-ready structures, corresponding with 69,526 CAS numbers. Simulation of Phase I metabolites resulted in 306,279 unique metabolites. QSAR predictions could be performed for 64,684 of the QSAR-ready structures, whereas information was retrieved from the CompTox Chemicals Dashboard for 59,739 CAS numbers out of 69,526 inquiries. CECscreen is incorporated in the in silico fragmentation approach MetFrag. Discussion The CECscreen database can be used to prioritize annotation of CECs measured in non-targeted HRMS, facilitating the large-scale detection of CECs in human samples for exposome research. Large-scale detection of CECs can be further improved by integrating the present database with resources that contain CECs (metabolites) and meta-data measurements, further expansion towards in silico and experimental (e.g. , MassBank) generation of MS/MS spectra, and development of bioinformatics approaches capable of using correlation patterns in the measured chemical features.
关键词：Annotation database ; High-resolution mass spectrometry ; Chemicals of emerging concern ; Exposome research