Veselkov Kirill A, Lindon John C, Ebbels Timothy M D, Crockford Derek, Volynkin Vladimir V, Holmes Elaine, Davies David B, Nicholson Jeremy K
Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anesthetics (SORA), Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London, UK.
Anal Chem. 2009 Jan 1;81(1):56-66. doi: 10.1021/ac8011544.
Chemical shift variation in small-molecule (1)H NMR signals of biofluids complicates biomarker information recovery in metabonomic studies when using multivariate statistical and pattern recognition tools. Current peak realignment methods are generally time-consuming or align major peaks at the expense of minor peak shift accuracy. We present a novel recursive segment-wise peak alignment (RSPA) method to reduce variability in peak positions across the multiple (1)H NMR spectra used in metabonomic studies. The method refines a segmentation of reference and test spectra in a top-down fashion, sequentially subdividing the initial larger segments, as required, to improve the local spectral alignment. We also describe a general procedure that allows robust comparison of realignment quality of various available methods for a range of peak intensities. The RSPA method is illustrated with respect to 140 (1)H NMR rat urine spectra from a caloric restriction study and is compared with several other widely used peak alignment methods. We demonstrate the superior performance of the RSPA alignment over a wide range of peaks and its capacity to enhance interpretability and robustness of multivariate statistical tools. The approach is widely applicable for NMR-based metabolic studies and is potentially suitable for many other types of data sets such as chromatographic profiles and MS data.
在代谢组学研究中，当使用多元统计和模式识别工具时，生物流体中小分子的（1）H NMR信号的化学位移变化会使生物标志物信息的提取变得复杂。当前的峰重新对齐方法通常耗时，或者以牺牲小峰位移精度为代价对齐主峰。我们提出了一种新颖的递归逐段峰对齐（RSPA）方法，以减少代谢组学研究中使用的多个（1）H NMR谱图中峰位置的变异性。该方法以自上而下的方式细化参考谱图和测试谱图的分割，根据需要依次细分初始的较大片段，以改善局部谱图对齐。我们还描述了一种通用程序，该程序允许在一系列峰强度下对各种可用方法的重新对齐质量进行稳健比较。通过一项热量限制研究中的140个（1）H NMR大鼠尿液谱图说明了RSPA方法，并将其与其他几种广泛使用的峰对齐方法进行了比较。我们证明了RSPA对齐在广泛的峰范围内具有卓越的性能，以及它增强多元统计工具的可解释性和稳健性的能力。该方法广泛适用于基于NMR的代谢研究，并且可能适用于许多其他类型的数据集，例如色谱图和MS数据。
