IDSL.UFA Assigns High-Confidence Molecular Formula Annotations for Untargeted LC/HRMS Data Sets in Metabolomics and Exposomics.
IDSL.UFA Assigns High-Confidence Molecular Formula Annotations for Untargeted LC/HRMS Data Sets in Metabolomics and Exposomics.
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DOI：
10.1021/acs.analchem.2c00563
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发表时间：
2022-10-04
影响因子：
7.4
通讯作者：
Barupal, Dinesh Kumar
中科院分区：
文献类型：
--
作者：
Baygi, Sadjad Fakouri;Banerjee, Sanjay K.;Chakraborty, Praloy;Kumar, Yashwant;Barupal, Dinesh Kumar
代谢组学和暴露组学中的非靶向LC/HRMS分析旨在表征生物样品中的小分子化学空间。为了从这些数据集获得最大的生物学洞察力，LC/HRMS峰应该用化学和功能信息进行注释，包括分子式、结构、化学类别和代谢途径。其中，分子式可以通过匹配基础电离化合物的理论和观测的同位素轮廓(MS1)来分配给LC/HRMS峰。为此，我们开发了代谢组学和暴露组学综合数据科学实验室-联合公式注释(IDSL.UFA)R包。在非靶向代谢组学验证测试中，IDSL.UFA将真阳性注释的54.31%-85.51%的分子式指定为最高命中率，前五个命中率为90.58%-100%。MS/MS数据也支持分子式注释。我们实施了新的策略来1)生成公式源及其理论同位素分布，2)优化个人和排列的峰值列表的公式命中排名，3)扩大基于IDSL的工作流，用于更大样本量的研究。UFA强调了数百种新的与怀孕有关的化合物，并建议在人类样本中存在氯化全氟三醚醇(Cl-PFTrEAs)。IDSL.UFA对于人类代谢组学和暴露组学研究是有用的，在这些研究中，我们需要将非靶向LC/HRMS数据集中的生物学见解的损失降至最低。UFA包可以在R cran库中找到，https://cran.r-project.org/package=IDSL.UFA.的详细文档和教程也可以在www.ufa.idsl.me上找到。
Untargeted LC/HRMS assays in metabolomics and exposomics aim to characterize the small molecule chemical space in a biospecimen. To gain maximum biological insights from these datasets, LC/HRMS peaks should be annotated with chemical and functional information including molecular formula, structure, chemical class and metabolic pathways. Among these, molecular formulas may be assigned to LC/HRMS peaks through matching theoretical and observed isotopic profiles (MS1) of the underlying ionized compound. For this, we have developed the Integrated Data Science Laboratory for Metabolomics and Exposomics – United Formula Annotation (IDSL.UFA) R package. In the untargeted metabolomics validation tests, IDSL.UFA assigned 54.31%–85.51% molecular formula for true positive annotations as the top hit, and 90.58%–100% within the top five hits. Molecular formula annotations were also supported by MS/MS data. We have implemented new strategies to 1) generate formula sources and their theoretical isotopic profiles 2) optimize the formula hits ranking for the individual and the aligned peak lists and 3) scale IDSL.UFA-based workflows for studies with larger sample sizes. Annotating the raw data for a publicly available pregnancy metabolome study using IDSL.UFA highlighted hundreds of new pregnancy related compounds, and also suggested presence of chlorinated perfluorotriether alcohols (Cl-PFTrEAs) in human specimens. IDSL.UFA is useful for human metabolomics and exposomics studies where we need to minimize the loss of biological insights in untargeted LC/HRMS datasets. The IDSL.UFA package is available in the R CRAN repository https://cran.r-project.org/package=IDSL.UFA. Detailed documentation and tutorials are also provided at www.ufa.idsl.me.
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影响因子：
7.4
作者：
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通讯作者：
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通讯作者：
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