Evaluation of Full-Resolution J-Resolved 1H NMR Projections of Biofluids for Metabonomics Information Retrieval and Biomarker Identification
Evaluation of Full-Resolution J-Resolved 1H NMR Projections of Biofluids for Metabonomics Information Retrieval and Biomarker Identification
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DOI：
10.1021/ac902443k
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发表时间：
2010-03-01
影响因子：
7.4
通讯作者：
Nicholson, Jeremy K.
中科院分区：
文献类型：
--
作者：
Fonville, Judith M.;Maher, Anthony D.;Nicholson, Jeremy K.
生物样品的光谱分析是代谢驱动的自上而下系统生物学的组成部分，可用于鉴定毒性和疾病的生物标志物。然而，最佳的生物标志物信息恢复和共振分配仍然对基于NMR的复杂混合物分析提出了重大挑战。当投影二维（2D）J分辨（JRES）NMR谱时实现的减少的信号重叠可以被利用来减轻这个问题，并且在这里，全分辨率H-1 JRES投影已经被评估为用于代谢筛选和生物标志物鉴定的工具。我们发现，可恢复的信息内容在JRES预测是本质上不同于传统的一维（1D）和Carr-Purcell-Meiboom-Gill（CPMG）光谱，因为高度分裂的多重峰和松弛编辑的过度表示减少的综合结果。全分辨率JRES光谱数据的主成分和相关分析表明，峰对齐是必要的。统计全相关光谱（STOCSY）的应用JRES预测提高了识别以前重叠的小分子共振在JRES H-1 NMR光谱，相比传统的1D和CPMG光谱。这些方法被证明使用半乳糖胺诱导的大鼠肝毒性研究，并表明，JRES预测有一个有用的和补充的作用，标准的一维实验在复杂的混合物分析，以改善生物标志物的识别。
Spectroscopic profiling of biological samples is an integral part of metabolically driven top-down systems biology and can be used for identifying biomarkers of toxicity and disease. However, optimal biomarker information recovery and resonance assignment still pose significant challenges in NMR-based complex mixture analysis. The reduced signal overlap as achieved when projecting two-dimensional (2D) J-resolved (JRES) NMR spectra can be exploited to mitigate this problem and, here, full-resolution H-1 JRES projections have been evaluated as a tool for metabolic screening and biomarker identification. We show that the recoverable information content in JRES projections is intrinsically different from that in the conventional one-dimensional (1D) and Carr-Purcell-Meiboom-Gill (CPMG) spectra, because of the combined result of reduction of the over-representation of highly split multiplet peaks and relaxation editing. Principal component and correlation analyses of full-resolution JRES spectral data demonstrated that peak alignment is necessary. The application of statistical total correlation spectroscopy (STOCSY) to JRES projections improved the identification of previously overlapped small molecule resonances in JRES H-1 NMR spectra, compaired to conventional 1D and CPMG spectra. These approaches are demonstrated using a galactosamine-induced hepatotoxicity study in rats and show that JRES projections have a useful and complementary role to standard one-dimensional experiments in complex mixture analysis for improved biomarker identification.