Simplify: A Mass Spectrometry Metabolomics Approach to Identify Additives and Synergists from Complex Mixtures
Simplify: A Mass Spectrometry Metabolomics Approach to Identify Additives and Synergists from Complex Mixtures
复制标题
DOI：
10.1021/acs.analchem.9b02377
复制
发表时间：
2019-09-03
影响因子：
7.4
通讯作者：
Cech, Nadja B.
中科院分区：
文献类型：
--
作者：
Caesar, Lindsay K.;Nogo, Sabina;Cech, Nadja B.
在从环境毒理学到药物发现等领域，确定多种化合物如何相互作用以扰乱生物系统至关重要。基于隔离的方法不能包含多成分的相互作用，例如协同作用。我们已经开发了一种名为“简化”的方法，它可以识别相互作用以实现生物效应的混合成分。Simplify结合了生物和质谱数据集，并使用“活性指数”来预测混合物的相互作用。以植物丹参为例，我们使用Simplify识别出四种有助于抗菌活性的单独成分，三种添加剂和一种增效剂。我们的研究是第一个能够在分离未知增效剂之前识别它们的研究，证明了Simplify工作流程预测复杂混合物生物效应关键因素的能力。“虽然在本研究中用于天然产物的发现，但这种方法有望在依赖混合物分析的多个学科中证明是有用的。
In fields ranging from environmental toxicology to drug discovery, it is critical to identify how multiple chemical compounds interact to perturb biological systems. Isolation-based approaches fail to incorporate multiconstituent interactions, such as synergy. We have developed an approach called "Simplify", which identifies mixture constituents that interact to achieve biological effects. Simplify combines biological and mass spectrometric data sets and uses an "activity index" to predict mixture interactions. Using the plant Salvia miltiorrhiza as a case study, we employed Simplify to identify four individual constituents that contribute to antimicrobial activity, three additives and one synergist. Our study is the first to enable identification of unknown synergists prior to isolating them, demonstrating the ability of the Simplify workflow to predict key contributors to the biological effect of a complex mixture. "While utilized for natural products discovery in this study, this approach is expected to prove useful across multiple disciplines that rely on mixture analysis.