Development of a multivariate statistical model to predict peroxisome proliferation in the rat, based on urinary 1H-NMR spectral patterns
Development of a multivariate statistical model to predict peroxisome proliferation in the rat, based on urinary 1H-NMR spectral patterns
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DOI：
10.1080/13547500400006005
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发表时间：
2004-07-01
期刊：
影响因子：
2.6
通讯作者：
Haselden, JN
中科院分区：
文献类型：
--
作者：
Connor, SC;Hodson, MP;Haselden, JN
这项工作的先前报告（Ringeissen et al. 2003）描述了使用核磁共振（NMR）波谱结合多元统计数据分析（MVDA）来识别Wistar Han大鼠过氧化物酶体增殖（PP）的新生物标志物。描述了大鼠过氧化物酶体增殖的两种潜在生物标志物，n -甲基烟酰胺（NMN）和n -甲基-4-吡啶酮-3-羧酰胺（4PY）。从这些结果推断，色氨酸-烟酰胺腺嘌呤二核苷酸（NAD(+)）途径与过氧化物酶体增殖相关，随后通过TaqMan(R)分析编码该途径中两个关键酶的相关基因，氨基羧酸盐-半醛脱羧酶（EC 4.1.1.45）和喹啉酸盐磷酸核糖基转移酶（EC 2.4.2.19），证实了这一假设。本研究的目的是进一步研究这些数据，并在核磁共振光谱中确定与PP同等相关的其他代谢物。MVDA偏最小二乘（PLS）模型的构建提供了比单独使用4PY和NMN水平更好的预测Wistar Han大鼠PP的模型。然后使用所得的Wistar Han大鼠预测模型来预测实验组Sprague Dawley大鼠在给予非诺贝特后的PP。模型预测了实验组所有斯普拉格-道利大鼠中PP的存在或不存在（高于任意阈值的2倍平均对照）。
A previous report of this work (Ringeissen et al. 2003) described the use of nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical data analysis (MVDA) to identify novel biomarkers of peroxisome proliferation ( PP) in Wistar Han rats. Two potential biomarkers of peroxisome proliferation in the rat were described, N-methylnicotinamide (NMN) and N-methyl-4-pyridone-3-carboxamide (4PY). The inference from these results was that the tryptophan-nicotinamide adenine dinucleotide (NAD(+)) pathway was altered in correlation with peroxisome proliferation, a hypothesis subsequently confirmed by TaqMan(R) analysis of the relevant genes encoding two key enzymes in the pathway, aminocarboxymuconate-semialdehyde decarboxylase (EC 4.1.1.45) and quinolinate phosphoribosyltransferase (EC 2.4.2.19). The objective of the present study was to investigate these data further and identify other metabolites in the NMR spectrum correlating equally with PP. MVDA Partial Least Squares (PLS) models were constructed that provided a better prediction of PP in Wistar Han rats than levels of 4PY and NMN alone. The resulting Wistar Han rat predictive models were then used to predict PP in a test group of Sprague Dawley rats following administration of fenofibrate. The models predicted the presence or absence of PP (above an arbitrary threshold of > 2-fold mean control) in all Sprague Dawley rats in the test group.