Comparison of GC-MS and GC×GC-MS in the analysis of human serum samples for biomarker discovery.
Comparison of GC-MS and GC×GC-MS in the analysis of human serum samples for biomarker discovery.
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DOI：
10.1021/pr5011923
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发表时间：
2015-04-03
影响因子：
4.4
通讯作者：
Zhang X
中科院分区：
文献类型：
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作者：
Winnike JH;Wei X;Knagge KJ;Colman SD;Gregory SG;Zhang X
我们比较了气相色谱飞行时间质谱 (GC-MS) 和综合二维气相色谱质谱 (GC×GC-MS) 在代谢物生物标志物发现方面的性能。在两个平台上分析了 109 份人类血清样本的代谢提取物，并出于质量控制 (QC) 的目的，每 9 份生物样本后分析一份合并血清样本。来自混合 QC 样品的实验数据表明，GC×GC-MS 平台在信噪比 SNR ≥ 50 下检测到的峰数量约为 GC-MS 平台的三倍，通过质谱匹配鉴定出的代谢物数量是 GC-MS 平台的三倍，谱图相似性评分 Rsim ≥ 600。在 GC-MS 数据集中，23 种代谢物在患者样品和对照样品之间具有统计学上显着的丰度变化，而 34 种代谢物在 GC-MS 数据集中检测到的峰数量是 GC-MS 平台的三倍。 GC×GC-MS数据集中的代谢物显示出统计学上显着的差异。在这两组代谢物生物标志物中，GC-MS 和 GC×GC-MS 数据集中均检测到了 9 种代谢物，对照组和患者样本组之间的丰度变化方向相同且幅度相似。手动验证表明，使用这两个平台发现的生物标志物数量的差异主要是由于GC-MS平台的色谱峰分辨率有限，这会导致严重的峰重叠，使得后续代谢物鉴定和定量的谱图解卷积变得困难。
We compared the performance of gas chromatography time-of-flight mass spectrometry (GC-MS) and comprehensive two-dimensional gas chromatography mass spectrometry (GC×GC-MS) for metabolite biomarker discovery. Metabolite extracts from 109 human serum samples were analyzed on both platforms with a pooled serum sample analyzed after every 9 biological samples for the purpose of quality control (QC). The experimental data derived from the pooled QC samples showed that the GC×GC-MS platform detected about three times as many peaks as the GC-MS platform at a signal-to-noise ratio SNR ≥ 50, and three times the number of metabolites were identified by mass spectrum matching with a spectral similarity score Rsim ≥ 600. Twenty-three metabolites had statistically significant abundance changes between the patient samples and the control samples in the GC-MS data set while 34 metabolites in the GC×GC-MS data set showed statistically significant differences. Among these two groups of metabolite biomarkers, nine metabolites were detected in both the GC-MS and GC×GC-MS data sets with the same direction and similar magnitude of abundance changes between the control and patient sample groups. Manual verification indicated that the difference in the number of the biomarkers discovered using these two platforms was mainly due to the limited resolution of chromatographic peaks by the GC-MS platform, which can result in severe peak overlap making subsequent spectrum deconvolution for metabolite identification and quantification difficult.