Ultrahigh-resolution 1H-13C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction
Ultrahigh-resolution 1H-13C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction
复制标题
DOI：
10.1021/ja068541x
复制
发表时间：
2007-04-25
影响因子：
15
通讯作者：
Wagner, Gerhard
中科院分区：
文献类型：
--
作者：
Hyberts, Sven G.;Heffron, Gregory J.;Wagner, Gerhard
为了全面评估白细胞提取物的代谢物水平，我们记录了细胞提取物的超高分辨率H-1-C-13HSQC核磁共振谱，其中显示了大量小分子的光谱特征。然而，这种光谱的常规获取是耗时的，并且阻碍了对多个样品的测量，这将是对代谢物浓度进行统计分析所必需的。在这里，我们展示了当使用非线性采样(NLS)和一种新的高保真前向最大熵(FM)重建算法时，可以在不损失频谱质量的情况下显著缩短测量时间。这种FM重建保留了所有测量的时域数据点，并通过迭代过程猜测丢失的数据点。这包括稀疏时间域数据集的离散傅立叶变换、谱熵的计算、多维熵梯度的确定以及用共轭梯度法计算丢失的时间域数据点的新值。由于该过程不改变测量数据点，因此它以高保真度再现信号强度，并且不存在动态范围问题。作为一个例子，我们测量了粒细胞提取物的代谢产物的自然丰度H-1-C-13HSQC谱。我们发现，在3.7天内线性记录4k复数增量的高分辨率H-1-C-13HSQC谱可以从七分之一的增量重建出来，这些增量具有几乎相同的光谱外观、不可区分的信号强度、可比甚至更低的均方根(RMS)和在无信号区测量的峰值噪声图案。因此，这种方法允许在记录线性采样光谱所需时间的一小部分内记录超高分辨率H-1-C-13HSQC光谱。
To obtain a comprehensive assessment of metabolite levels from extracts of leukocytes, we have recorded ultrahigh-resolution H-1-C-13 HSQC NMR spectra of cell extracts, which exhibit spectral signatures of numerous small molecules. However, conventional acquisition of such spectra is time-consuming and hampers measurements on multiple samples, which would be needed for statistical analysis of metabolite concentrations. Here we show that the measurement time can be dramatically reduced without loss of spectral quality when using nonlinear sampling (NLS) and a new high-fidelity forward maximum-entropy (FM) reconstruction algorithm. This FM reconstruction conserves all measured time-domain data points and guesses the missing data points by an iterative process. This consists of discrete Fourier transformation of the sparse time-domain data set, computation of the spectral entropy, determination of a multidimensional entropy gradient, and calculation of new values for the missing time-domain data points with a conjugate gradient approach. Since this procedure does not alter measured data points, it reproduces signal intensities with high fidelity and does not suffer from a dynamic range problem. As an example we measured a natural abundance H-1-C-13 HSQC spectrum of metabolites from granulocyte cell extracts. We show that a high-resolution H-1-C-13 HSQC spectrum with 4k complex increments recorded linearly within 3.7 days can be reconstructed from one-seventh of the increments with nearly identical spectral appearance, indistinguishable signal intensities, and comparable or even lower root-mean-square (rms) and peak noise patterns measured in signal-free areas. Thus, this approach allows recording of ultrahigh resolution H-1-C-13 HSQC spectra in a fraction of the time needed for recording linearly sampled spectra.