McEachran Andrew D, Chao Alex, Al-Ghoul Hussein, Lowe Charles, Grulke Christopher, Sobus Jon R, Williams Antony J
Oak Ridge Institute for Science and Education (ORISE) Participant, 109 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Metabolites. 2020 Jun 23;10(6):260. doi: 10.3390/metabo10060260.
Software applications for high resolution mass spectrometry (HRMS)-based non-targeted analysis (NTA) continue to enhance chemical identification capabilities. Given the variety of available applications, determining the most fit-for-purpose tools and workflows can be difficult. The Critical Assessment of Small Molecule Identification (CASMI) contests were initiated in 2012 to provide a means to evaluate compound identification tools on a standardized set of blinded tandem mass spectrometry (MS/MS) data. Five CASMI contests have resulted in recommendations, publications, and invaluable datasets for practitioners of HRMS-based screening studies. The US Environmental Protection Agency's (EPA) CompTox Chemicals Dashboard is now recognized as a valuable resource for compound identification in NTA studies. However, this application was too new and immature in functionality to participate in the five previous CASMI contests. In this work, we performed compound identification on all five CASMI contest datasets using Dashboard tools and data in order to critically evaluate Dashboard performance relative to that of other applications. CASMI data was accessed via the CASMI webpage and processed for use in our spectral matching and identification workflow. Relative to applications used by former contest participants, our tools, data, and workflow performed well, placing more challenge compounds in the top five of ranked candidates than did the winners of three contest years and tying in a fourth. In addition, we conducted an in-depth review of the CASMI structure sets and made these reviewed sets available via the Dashboard. Our results suggest that Dashboard data and tools would enhance chemical identification capabilities for practitioners of HRMS-based NTA.
用于基于高分辨率质谱（HRMS）的非靶向分析（NTA）的软件应用程序不断提升化学物鉴定能力。鉴于可用应用程序种类繁多，确定最适用的工具和工作流程可能具有挑战性。小分子鉴定关键评估（CASMI）竞赛始于2012年，旨在提供一种方法，以一组标准化的盲态串联质谱（MS/MS）数据来评估化合物鉴定工具。五届CASMI竞赛为基于HRMS的筛查研究人员带来了建议、出版物以及宝贵的数据集。美国环境保护局（EPA）的综合毒性化学品数据库现已被公认为NTA研究中化合物鉴定的宝贵资源。然而，该应用程序在功能上过于新颖和不成熟，无法参与此前的五届CASMI竞赛。在这项工作中，我们使用数据库工具和数据对所有五届CASMI竞赛数据集进行了化合物鉴定，以便严格评估数据库相对于其他应用程序的性能。通过CASMI网页获取CASMI数据，并对其进行处理，以用于我们的光谱匹配和鉴定工作流程。相对于往届竞赛参与者使用的应用程序，我们的工具、数据和工作流程表现出色，在排名靠前的候选化合物中，我们将更多的挑战性化合物排在前五位，超过了三个竞赛年份的获胜者，并在第四个年份持平。此外，我们对CASMI结构集进行了深入审查，并通过数据库提供这些经过审查的结构集。我们的结果表明，数据库数据和工具将增强基于HRMS的NTA研究人员的化学物鉴定能力。
