Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
1] Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK. [2] Present address: Max Planck Institute for Marine Microbiology, Bremen, Germany.
Nat Protoc. 2014;9(6):1416-27. doi: 10.1038/nprot.2014.090. Epub 2014 May 22.
Data processing for 1D NMR spectra is a key bottleneck for metabolomic and other complex-mixture studies, particularly where quantitative data on individual metabolites are required. We present a protocol for automated metabolite deconvolution and quantification from complex NMR spectra by using the Bayesian automated metabolite analyzer for NMR (BATMAN) R package. BATMAN models resonances on the basis of a user-controllable set of templates, each of which specifies the chemical shifts, J-couplings and relative peak intensities for a single metabolite. Peaks are allowed to shift position slightly between spectra, and peak widths are allowed to vary by user-specified amounts. NMR signals not captured by the templates are modeled non-parametrically by using wavelets. The protocol covers setting up user template libraries, optimizing algorithmic input parameters, improving prior information on peak positions, quality control and evaluation of outputs. The outputs include relative concentration estimates for named metabolites together with associated Bayesian uncertainty estimates, as well as the fit of the remainder of the spectrum using wavelets. Graphical diagnostics allow the user to examine the quality of the fit for multiple spectra simultaneously. This approach offers a workflow to analyze large numbers of spectra and is expected to be useful in a wide range of metabolomics studies.
一维核磁共振(1D NMR)谱的数据处理是代谢组学和其他复杂混合物研究的一个关键瓶颈,特别是在需要单个代谢物的定量数据的情况下。我们提出了一种使用贝叶斯自动代谢物分析器用于 NMR(BATMAN)R 包从复杂 NMR 谱中自动进行代谢物解卷积和定量的方案。BATMAN 根据用户可控制的模板集对共振进行建模,每个模板指定单个代谢物的化学位移、J 耦合和相对峰强度。允许峰在谱之间稍微移动位置,并允许峰宽根据用户指定的量变化。未被模板捕获的 NMR 信号通过小波进行非参数建模。该方案涵盖了设置用户模板库、优化算法输入参数、改进峰位置的先验信息、质量控制和输出评估。输出包括命名代谢物的相对浓度估计值以及相关的贝叶斯不确定性估计值,以及使用小波对光谱的其余部分进行拟合。图形诊断允许用户同时检查多个光谱的拟合质量。该方法提供了一种分析大量光谱的工作流程,预计在广泛的代谢组学研究中非常有用。