氢谱磁共振代谢组学在2型糖尿病特征代谢物监测中的应用

目的应用氢谱磁共振(~1H-NMR)代谢组学方法研究2型糖尿病(T2DM)患者尿液中小分子代谢物代谢轮廓的变化。方法选择T2DM患者98例及健康对照组82例,利用~1H-NMR方法检测尿液的代谢轮廓,结合偏最小二乘判别分析法的模式识别分析方法,比较两组尿液中小分子代谢物差异。结果尿液的偏最小二乘判别分析法得分图显示与T2DM有关的特征代谢物包括乙酸、乳酸、牛磺酸、乙酰乙酸、葡萄糖、丙氨酸、甲基丙二酸、肌酐、柠檬酸、三甲胺等。结论糖代谢紊乱、氧化应激、氨基酸及脂类代谢异常、维生素缺乏在T2DM及其并发症的发生发展中起到重要作用。~1H-NMR代谢组学方法,可以全景监测小分子代谢终端产物的变化,符合T2DM代谢性疾病的特点

A New Filter Algorithm for Random Valued Impulse Noise

文章详细分析了随机值脉冲噪声污染图像的局部灰度统计特征,定义了一种噪声可信度的估计函数—灰度等级共现几率,并在此基础上提出了共现几率极小的中值滤波算法。算法模拟生物视觉在注视过程中的变分辨率特性,以不同分辨率对噪声进行多层次的定位及滤波。实验结果表明,该文算法可以有效地滤除噪声,并较好地保留图像的边缘细节信息,其滤波效果比其它算法更接近理想的中值滤波,尤其是对于噪声高度污染的情况。The locally statistical characters of the random valued impulse noise image are studied in detail.And the gray-levels occurrence probability is defined to measure the noise reliability of the image pixels.Then a nonlinear algorithm called Minimum Occurrence Probability Median(MOPM) filter is presented to remove the random valued impulsenoise from grayscale images.The presented algorithm performs noise detection and filtering at multiple resolutions based on the biological concept of foveal vision.Computer simulation results show that the presented algorithm outperforms the other filtering algorithms in the aspects of filtering ability,adaptability and details preserving ability,which is very close to the ideal median filter,especially for highly corrupted images.国家自然科学基金资助项目(编号:60371044

Metabolic Response of Basal Ganglia in Copper-laden Rat to Gandouling Based on ~1H NMR Spectroscopy

采用核磁共振氢谱(1H NMR)技术与多元统计分析相结合的方法,对肝豆灵对大鼠基底节铜损伤的调节机制进行研究。24只雄性Wistar大鼠随机分为正常组、模型组和肝豆灵组,每组8只,以铜负荷法造模。从造模第7周开始,肝豆灵组大鼠以肝豆灵灌胃。数据分析显示:与正常组比较,模型组的基底节细胞凋亡指数显著增高(p<0.01);基底节组织中的谷氨酰胺、尿苷、苏氨酸含量升高(p<0.05),甘露醇、腺苷、N-乙酰天冬氨酸、谷氨酸、N-乙酰谷氨酸(NAG)、天冬酰胺、乙酸、天冬氨酸、肌醇、三磷酸腺苷(ATP)含量降低(p<0.05);与模型组相比,肝豆灵组的基底节细胞凋亡指数显著降低(p<0.01);基底节组织中的谷氨酰胺、尿苷、乙酸、天冬氨酸含量降低(p<0.05),甘露醇、腺苷、苏氨酸、N-乙酰天冬氨酸、谷氨酸、N-乙酰谷氨酸、天冬酰胺、肌醇、ATP含量升高(p<0.05)。研究结果表明,肝豆灵可影响铜负荷大鼠基底节的代谢,对铜损伤具有一定的修复作用,其机制可能是通过调节氨的解毒和兴奋性氨基酸类神经递质的代谢,干预能量代谢,恢复神经元和神经胶质细胞功能。1H NMR spectroscopy combined with multivariate statistical method was introduced in this paper to explore the regulation effect of Gandouling on basal ganglia injury in copper-laden rats. 24 male Wistar rats were randomly divided into control group,model group and Gandouling group,with8 rats in each group. The rat model was established by copper-laden method. From the 7th week of modeling,Gandouling group was given Gandouling formula via gavage. Compared with the control group,the index of apoptosis cells in basal ganglia of model group increased significantly( p < 0. 01),and glutamine,uridine and threonine in basal ganglia were increased( p < 0. 05) while mannitol,adenosine,N-acetylaspartate, glutamate, N-acetylglutamine asparagine, acetate, aspartate, myoinositol and ATP were decreased( p < 0. 05). Compared with the model group,the index of apoptosis cells in basal ganglia of Gandouling group was significantly decreased( p < 0. 01),and glutamine,uridine,acetate and aspartate were reduced( p < 0. 05) while mannitol, adenosine, threonine,N-acetylaspartate,glutamate,N-acetylglutamine,asparagine,myo-inositol and ATP were elevated( p < 0. 05). The results showed that Gandouling could influence the metabolism of basal ganglia in copper-laden rats,which has a certain therapeutic effect on damage caused by copper. The mechanism may be restoration of the functions of neurons and glial cells,through adjusting the detoxification of ammonia and metabolism of excitatory amino acid neurotransmitter and interfering the energy metab-olism.国家自然科学基金(81202691,81201143,81371639);; 福建省自然科学基金(2015Y0032

Comparison of mechanism for copper-excretion between Gandouling Tablets and penicillamine by metabonomics

目的探讨肝豆灵片(大黄、黄芩、黄连、半枝莲等)和青霉胺对大鼠的代谢物,以比较两者排铜机制异同。方法适应性饲养1周后,大鼠被随机分为对照组、模型组、肝豆灵组、青霉胺组。造模结束后,取各组大鼠血清样品分析其核磁共振谱峰。结果模型组大鼠血清乳酸、糖蛋白、肌酸、肌酐、谷氨酰胺、精氨酸的量升高,葡萄糖、甜菜碱、胆碱、磷酸胆碱、脂质的量降低;青霉胺组大鼠血清葡萄糖、甜菜碱、胆碱、胆碱磷酸、脂质的量升高,糖蛋白、乳酸、肌酸、肌酐、谷氨酰胺的量降低;肝豆灵组大鼠血清3-羟基丁酸、亮氨酸、异亮氨酸、缬氨酸、胆碱、胆碱磷酸、葡萄糖、脂质的量升高,谷氨酰胺、乳酸、肌酸、肌酐、精氨酸的量降低。结论青霉胺与肝豆灵均可明显调节铜负荷大鼠的葡萄糖、乳酸、肌酸、肌酐、胆碱、磷酸胆碱、谷氨酰胺和脂质向正常范围回归的趋势。而肝豆灵片还可调节鸟氨酸循环、支链氨基酸、3-羟基丁酸及氨的代谢。AIM To apply metabonomics to the exploration of differences in mechanism for copper-excretion between Gandouling Tablets( Rheum officinale Baill.,Scutellaria baicalensis Georgi,Coptis chinensis Franch.,Scutellaria barbata D. Don,etc.) and penicillamine. METHODS After adaptive breeding for one week,the tested rats were randomly divided into four groups, including control, model, Gandouling Tablets and penicillamine group. After modeling,the sera of all groups were analyzed by1H-NMR spectroscopy. RESULTS The model group showed increased levels of lactate, glutamine, glycoprotein, creatine, creatinine and arginine,together with decreased levels of glucose,betaine,choline,phosphocholine and lipid. Penicillamine group had increased levels of glucose,betaine,choline,phosphocholine and lipid,together with decreased levels of glutamine,glycoprotein,lactate,creatine and creatinine. While Gandouling Tablets increased 3-hydroxybutyrate,leucine, isoleucine, valine, choline, phosphocholine, glucose and lipid, but decreased glutamine,lactate,creatine,creatinine and arginine. CONCLUSION There is a similarity of mechanism for copper excretion between Gandouling Tablets and penicillamine, mainly in the metabolic regulation of glutamine, lactate,creatine,creatinine, glucose, choline, phosphocholine and lipid returning to normal. Moreover,Gandouling Tablets can regulate the metabolisms of ornithine cycle,3- hydroxybutyric acid and branched chain amino acids.国家自然科学基金青年基金资助(81202691);; 安徽省高校自然科学基金重点项目(KJ2012Z228);; 安徽省高校博士后岗位项目(2013年

New Algorithm for Peak Alignment of Nuclear Magnetic Resonance

谱峰对齐是基于核磁共振的代谢组学数据预处理过程中的一个重要环节,谱峰对齐效果直接影响后续的多变量统计分析。提出了一种基于高斯平滑的谱峰对齐算法(gPA)。算法通过调节高斯卷积函数的窗口大小,实现波谱信号的多尺度平滑,进而由粗到细、逐步实现波谱信号的谱峰对齐。真实的核磁共振波谱实验结果表明:gPA算法可以快速准确地实现谱峰对齐,且对齐后的波谱信号在平均相似度、后续统计模型的解释能力等综合性能上的表现明显优于相关优化解缠(COW)和多尺度谱峰对齐(MSPA)等常用谱峰对齐算法。Peak alignment is an important step during metabolomics data pretreatment process based on nuclear magnetic resonance(NMR) and its effect plays a direct role on subsequent multivariate statistical analysis.A peak alignment algorithm based on Gaussian smoothing(GPA) is presented.Spectrum signals can be smoothed on multiple scales by adjusting sizes of the windows of Gaussian convolution function.And peak alignment can be realized step by step from coarse to fine.The true experiment results of NMR spectrum show that peak alignment can be realized quickly and accurately by GPA algorithm.Comparing with common peak alignment algorithms such as correlation optimized warping(COW) and multi-scale peak alignment(MSPA),the aligned spectrum signals are superior at integrated performances such as average similarity and explanation performances of subsequent statistical models obviously.国家自然科学基金(81171331;81201143); 中央高校基本科研业务费专项资金(2011121046

Detection of the permutation symmetry in pattern sets

Symmetry is a powerful tool to reduce the freedom degrees of a system. But the applicability of the symmetry tool strongly depends on the ability to calculate the symmetries of the system. There exists an interesting algorithmic problem to search for the symmetry of a high-dimensional system. In this paper, a genetic algorithm-based permutation symmetry detection approach is proposed for pattern set. Firstly, the permutation symmetry distance (PSD) is defined to measure the similarity of a pattern set before and after being transformed by a permutation operator. Secondly, the permutation symmetry detection problem is converted into an optimization problem by taking the PSD as a fitness function. Lastly, a genetic algorithm-based approach is designed for the symmetry detection problem. Computer simulation results are also given for five pattern sets of different dimensionality, which show the efficiency and speediness of the proposed detection approach, especially in high-dimensional cases

Metabolomics Data Filtering Method Based on PCA

代谢组学数据不可避免地受到各种刺激因素的作用,如何降低干扰因素的影响是代谢组学数据预处理的一个重要任务。详细分析了代谢组学数据方差的构成及其在特征空间中的分布特点,并在此基础上提出一种滤除未知干扰因素的新方法,提高感兴趣因素的显著性。文中采用真实的代谢组学数据验证新滤波算法的有效性,并与正交信号校正(OrTHOgOnAl SIgnAlCOrrECTIOn,OSC)方法进行比较。实验结果表明,新滤波方法可以在抑制未知干扰因素影响的同时,较好地保留感兴趣因素信息以及生物体内在的个体差异信息,降低模型发生过拟合的危险,使后续的统计分析结果更可靠。The metabolomics dataset is disturbed by various stimuli inevitably.The main task for metabolo mics data preprocessing is to reduce the impacts of the disturbing factors.In present work,the formation of data variance and their distribution in feature space are analyzed.Furthermore,a new method to filtrate unknown disturb ing factors is proposed and the significance of interesting factors is improved.The efficiency of the new filtering al gorithm is estimated by real metabolomics dataset.Comparing with orthogonal signal correction(OSC) method,the experiment shows that the new method is superior in reducing unknown disturbing factors and retaining useful in formation and intrinsic individual differences in organisms.In addition,it can also prevent the overfitting of model and make the subsequent statistical analysis more reliable.国家自然科学基金(81171331;11175149);中央高校基本科研业务费专项资金(2011121046

Toxicity study of oral vanadyl sulfate by NMR-based metabonomic

Vanadium compounds have been believed to be ideal drugs for diabetes biological therapy in future, but they suffer setback for the potential toxicity now. Toxicity study is necessary for vanadyl drugs development. This paper investigated the toxicity effects of vanadyl sulfate (VOSO4) oral administration in male Wistar rats using H-1 NMR-based metabonomic analysis and clinical biochemical analysis. Rat urine were collected and their H-1 NMR spectra were acquired, and then subjected to multi-variable statistical analysis. Compared to control groups, urinary excretion of lactate, TMAO, creatinine, taurine and hippurate increased following VOSO4 dosing, with concomitant decrease in the level of acetate and succinate. The dosed groups can be readily discriminated from the control groups by principle component analysis. The results showed that VOSO4 can affect energy metabolism process, interrupted intestinal microfloral metabolism, and induced liver and kidney injury. NMR-based metabonomic can offer additional information to traditional clinical chemistry in the sensitivity and specificity of results obtained

Compositional Quantitation and Brand Identification of Beer via NMR Approach Combined with Multivariate Statistical Analysis

利用核磁共振技术检测福建产青岛、雪花、雪津麦之初和惠泉一麦等4种不同品牌啤酒的化学组分,结合多元统计方法分析不同啤酒的主成分差异,获得麦芽糖、葡萄糖、丙氨酸、乙酸等26种主要差异组分。并结合2种重要风味物质甘氨酸、丙酮酸,定量分析这28种主要成分,获得不同类型啤酒之间的组成差异及它们对啤酒风味的影响;进而建立啤酒的Fisher判别模型,实现不同品牌啤酒的鉴别。本研究可以检测不同来源啤酒样品的差异化学成分及含量,又可为其他酒类的鉴定分类提供参考。In this study, the chemical components of four beer samples of different brands including Tsingtao, Snow, Xuejin and Huiquan were quantitatively analyzed using NMR spectroscopy, and their differential components were identified by multivariate statistical analysis. 26 differential components were obtained, including maltose, glucose, alanine and organic acids. Quantitative analysis of the 26 components plus 2 important flavoring components glycine and pyruvate acid were carried out to confirm the compositional differences between these four kinds of beer and to understand their influence on the special flavor of beer. Furthermore, Fisher classification discriminant model was successfully established for the identification of beer of different brands. This study provided a new method to detect the chemical components and their content in beer of different brands, and a useful reference for the classification of other alcoholic drinks.国家自然科学基金项目(31372546,81371639);; 福建省自然科学基金项目(2014J01247,2015Y0032);; 中央高校基本科研业务费项目(20720150018

(1)H NMR-based metabonomics study of urine and serum samples from diabetic db/db mice

A metabonomics approach based on high resolution (1)H NMR spectroscopy was applied to investigate the metabolite fingerprints in urine and serum samples from db/db mice of 8 weeks old, an animal model of type 2 diabetes mellitus (T2DM). Both NMR spectra and metabonomics results were discussed and the variations on related metabolic pathway were analyzed. The urinary excretions of diabetic mice have elevated levels of citrate, alanine, acetate, TMAO, hippurate, taurine, creatinine, succinate, pyruvate, glycine in addition to evident increase of glucose compared to the control ones. The metabolic variation in serum samples of db/db mice is marked by the increases of lactate, 3-hydroxybutyrate, glutamine, glutamate and choline and the decreases of leucine and valine. These results indicate that NMR-based metabonomics is an efficient approach for investigating the subtle metabolic alterations in urine and serum from diabetic mice and the findings of the characteristic metabolites would be helpful for early diagnosis and prevention of T2DM and its related complications