Natural products (or specialized metabolites) are historically the main source of new drugs. However, the current drug discovery pipelines require miniaturization and speeds that are incompatible with traditional natural product research methods, especially in the early stages of the research. This article introduces the NP³ MS Workflow, a robust open-source software system for liquid chromatography–tandem mass spectrometry (LC–MS/MS) untargeted metabolomic data processing and analysis, designed to rank bioactive natural products directly from complex mixtures of compounds, such as bioactive biota samples. NP³ MS Workflow allows minimal user intervention as well as customization of each step of LC–MS/MS data processing, with diagnostic statistics to allow interpretation and optimization of LC–MS/MS data processing by the user. NP³ MS Workflow adds improved computing of the MS² spectra in an LC–MS/MS data set and provides tools for automatic [M + H]⁺ ion deconvolution using fragmentation rules; chemical structural annotation against MS² databases; and relative quantification of the precursor ions for bioactivity correlation scoring. The software will be presented with case studies and comparisons with equivalent tools currently available. NP³ MS Workflow shows a robust and useful approach to select bioactive natural products from complex mixtures, improving the set of tools available for untargeted metabolomics. It can be easily integrated into natural product-based drug-discovery pipelines and to other fields of research at the interface of chemistry and biology.

中文翻译：

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NP3 MS 工作流程：一种开源软件系统，可利用非靶向代谢组学进行基于天然产物的药物发现

天然产物（或专门的代谢物）历来是新药的主要来源。然而，当前的药物发现管道需要小型化和速度，这与传统的天然产物研究方法不兼容，特别是在研究的早期阶段。本文介绍了 NP ³ MS Workflow，这是一个强大的开源软件系统，用于液相色谱-串联质谱 (LC-MS/MS) 非靶向代谢组数据处理和分析，旨在直接对复杂的化合物混合物中的生物活性天然产物进行排序，例如具有生物活性的生物样本。 NP ³ MS 工作流程允许最少的用户干预以及定制 LC-MS/MS 数据处理的每个步骤，并具有诊断统计数据，允许用户解释和优化 LC-MS/MS 数据处理。 NP ³ MS 工作流程改进了LC–MS/MS 数据集中MS ²谱图的计算，并提供了使用碎片规则自动 [M + H] ^{+离子解卷积的工具；针对 MS 2}数据库的化学结构注释；以及用于生物活性相关评分的前体离子的相对定量。该软件将提供案例研究以及与当前可用的同等工具的比较。 NP ³ MS 工作流程展示了一种从复杂混合物中选择生物活性天然产物的稳健且有用的方法，改进了可用于非靶向代谢组学的工具集。它可以轻松集成到基于天然产物的药物发现管道以及化学和生物学界面的其他研究领域。