Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard
Identifying known unknowns using the US EPA's CompTox Chemistry Dashboard
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DOI：
10.1007/s00216-016-0139-z
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发表时间：
2017-03-01
影响因子：
4.3
通讯作者：
Williams, Antony J.
中科院分区：
文献类型：
--
作者：
McEachran, Andrew D.;Sobus, Jon R.;Williams, Antony J.
使用高分辨率质谱观察到的化学特征可以通过搜索分子式和单同位素质量，然后使用适当的相关性标准对命中进行排序，使用在线化学参考数据库来初步识别。最有可能的候选“已知未知物”是那些调查人员未知但包含在参考数据库或文献来源中的化学物质，当按相关数据源的数量排序时，它们会上升到化学物质列表的顶部。美国 EPA 的 CompTox Chemistry Dashboard 是一个专门用于化学和计算毒理学研究的免费资源，包含超过 720,000 种与环境健康科学相关的化学品。在这项研究中，根据在线 ChemSpider 数据库（质谱学家使用的主要资源之一）的性能，评估了仪表板识别已知未知物质的性能，使用了同行评审文献中报告的多个先前研究的数据集，总计 162 种化学物质。这些化学物质通过分子式和单同位素质量搜索两种应用程序进行了检查，然后根据相关参考文献或数据源对候选化合物进行排序。使用仪表板时，较高比例的化学品排在顶部位置，这表明该应用程序在使用数据源排名识别已知未知物方面比 ChemSpider 具有优势。正在开发其他方法，作为 CompTox 化学仪表板的一部分纳入非目标分析工作流程。这项工作通过显着改进非目标化学品识别，展示了仪表板在暴露评估和风险决策中的潜力。
Chemical features observed using high-resolution mass spectrometry can be tentatively identified using online chemical reference databases by searching molecular formulae and monoisotopic masses and then rank-ordering of the hits using appropriate relevance criteria. The most likely candidate "known unknowns," which are those chemicals unknown to an investigator but contained within a reference database or literature source, rise to the top of a chemical list when rank-ordered by the number of associated data sources. The U.S. EPA's CompTox Chemistry Dashboard is a curated and freely available resource for chemistry and computational toxicology research, containing more than 720,000 chemicals of relevance to environmental health science. In this research, the performance of the Dashboard for identifying known unknowns was evaluated against that of the online ChemSpider database, one of the primary resources used by mass spectrometrists, using multiple previously studied datasets reported in the peer-reviewed literature totaling 162 chemicals. These chemicals were examined using both applications via molecular formula and monoisotopic mass searches followed by rank-ordering of candidate compounds by associated references or data sources. A greater percentage of chemicals ranked in the top position when using the Dashboard, indicating an advantage of this application over ChemSpider for identifying known unknowns using data source ranking. Additional approaches are being developed for inclusion into a non-targeted analysis workflow as part of the CompTox Chemistry Dashboard. This work shows the potential for use of the Dashboard in exposure assessment and risk decision-making through significant improvements in non-targeted chemical identification.