Comparison of analytical mathematical approaches for identifying key nuclear magnetic resonance spectroscopy biomarkers in the diagnosis and assessment of clinical change of diseases.

Comparison of analytical mathematical approaches for identifying key nuclear magnetic resonance spectroscopy biomarkers in the diagnosis and assessment of clinical change of diseases.
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在诊断和评估疾病的临床变化中,比较了鉴定关键的核磁共振光谱生物标志物的分析数学方法的比较。

DOI:
10.1002/cne.22365
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发表时间:
2010-10-15
期刊:
The Journal of comparative neurology
影响因子:
--
通讯作者:
Low WC
Low WC
中科院分区:
其他
文献类型:
--
作者:
Nikas JB;Keene CD;Low WC

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核磁共振(NMR)光谱是一种快速发展的技术,可用于评估活体动物的组织代谢概况。目前,还没有开发出1)系统地鉴定可用作诊断疾病和监测疾病进展的生物标志物的关键化学改变的概况;和2)数学地评估潜在生物标志物的诊断能力的方法。为了解决这个问题,我们已经评估了采用受试者工作特征(ROC)曲线分析,线性判别分析和逻辑回归分析的数学方法,以系统地从NMR光谱中识别具有出色诊断能力的关键生物标志物,并可准确地用于疾病诊断和监测。为了验证我们的数学方法,我们研究了13只患有亨廷顿病的R6/ 2转基因小鼠以及17只野生型(WT)小鼠的17种代谢物的纹状体浓度,这些代谢物是通过体内质子NMR光谱(9.4特斯拉)获得的。我们基于上述三种数学方法开发了诊断生物标志物模型和临床变化评估模型,并对所有模型进行了测试,首先使用30只原始小鼠,然后使用31只未知小鼠。他们的预测结果与基因分型的金标准进行了比较。所有模型均正确诊断了所有30只原始小鼠(17只WT和13只R6/2)和所有31只未知小鼠(20只WT和11只R6/2),阳性似然比接近无穷大[1/0(→ ∞)],阴性似然比等于零[0/1 = 0]。
Nuclear magnetic resonance (NMR) spectroscopy is a rapidly emerging technology that can be used to assess tissue metabolic profile in the living animal. At the present time, no approach has been developed 1) to systematically identify profiles of key chemical alterations that can be used as biomarkers to diagnose diseases and to monitor disease progression; and 2) to assess mathematically the diagnostic power of potential biomarkers. To address this issue, we have evaluated mathematical approaches that employ receiver operating characteristic (ROC) curve analysis, linear discriminant analysis, and logistic regression analysis to systematically identify key biomarkers from NMR spectra that have excellent diagnostic power and can be used accurately for disease diagnosis and monitoring. To validate our mathematical approaches, we studied the striatal concentrations of 17 metabolites of 13 R6/ 2 transgenic mice with Huntington's disease, as well as those of 17 wild-type (WT) mice, which were obtained via in vivo proton NMR spectroscopy (9.4 Tesla). We developed diagnostic biomarker models and clinical change assessment models based on our three aforementioned mathematical approaches, and we tested all of them, first, with the 30 original mice and, then, with 31 unknown mice. Their prediction results were compared with genotyping—the gold standard. All models correctly diagnosed all of the 30 original mice (17 WT and 13 R6/2) and all of the 31 unknown mice (20 WT and 11 R6/2), with a positive likelihood ratio approximating infinity [1/0 (→ ∞)], and with a negative likelihood ratio equal to zero [0/1 = 0].
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