Simulated-to-real Benchmarking of Acquisition Methods in Metabolomics
Simulated-to-real Benchmarking of Acquisition Methods in Metabolomics
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DOI：
10.1101/2023.01.12.523759
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发表时间：
2023-01
期刊：
影响因子：
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通讯作者：
Joe Wandy;Ross McBride;Simon Rogers;Nikolaos Terzis;S. Weidt;J. V. D. van der Hooft;K. Bryson;Rónán Daly;Vinny Davies
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文献类型：
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作者：
Joe Wandy;Ross McBride;Simon Rogers;Nikolaos Terzis;S. Weidt;J. V. D. van der Hooft;K. Bryson;Rónán Daly;Vinny Davies
在非靶向液相色谱串联质谱（LC-MS/MS）代谢组学分析中，广泛采用数据依赖和数据独立采集模式（DDA和DIA）获取MS2光谱。尽管它们被广泛使用，但很少有人尝试系统地比较它们的性能，这是由于与真实实验数据进行比较的困难和成本，这是由于缺乏基础真理，以及运行大量收购所涉及的成本。在这里，我们提出了这两种采集方法的系统的计算机比较。为此，我们用DIA模块扩展了虚拟代谢组学质谱仪（ViMMS）框架。结果表明，这些方法的性能随共洗脱离子的平均数量而变化，这是最重要的因素。在低数值时，DIA优于DDA，但在高数值时，DDA具有优势，因为DIA不再能够处理大量重叠的离子色谱。仿真结果在实际质谱仪上得到进一步验证，表明使用ViMMS可以很好地将仿真结果转化为现实世界。在ViMMS中嵌入这项工作还允许研究人员轻松模拟DDA和DIA LC-MS/MS运行，在实际仪器上验证它们，并可能原型化结合两种方法特点的新方法。我们相信这项工作为参与代谢组学数据采集的科学家选择DIA或DDA提供了有用的指导。
Data-Dependent and Data-Independent Acquisition modes (DDA and DIA, respectively) are both widely used to acquire MS2 spectra in untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolomics analyses. Despite their wide use, little work has been attempted to systematically compare their performance due to the difficulty and cost of performing comparisons with real experimental data due to the lack of ground truth and the costs involved in running large number of acquisitions. Here, we present a systematic in-silico comparison of these two acquisition methods. To do so, we extended our Virtual Metabolomics Mass Spectrometer (ViMMS) framework with a DIA module. Our results show that the performance of these methods varies with the average number of co-eluting ions as the most important factor. At low numbers, DIA outperforms DDA, but at higher numbers, DDA has an advantage as DIA can no longer deal with the large amount of overlapping ion chromatograms. Results from simulation were further validated on an actual mass spectrometer, demonstrating that using ViMMS we can draw conclusions from simulation that translate well into the real world. Embedding this work within ViMMS also allows for researchers to easily simulate DDA and DIA LC-MS/MS runs, validate them on actual instrument, and potentially prototype novel methods that best combine the characteristics of both approaches. We believe that this work provides a useful guide to the choice of DIA or DDA for scientists involved in metabolomics data acquisition.