HIV感染者口腔代謝物變化與CD4水平的關(guān)系
發(fā)布時間：2018-08-02 20:51
【摘要】：[目的]口腔代謝產(chǎn)物的改變可用于疾病狀態(tài)和/或治療耐受的診斷標志,因此,分析口腔代謝物特征有助于發(fā)現(xiàn)HIV疾病進程的預(yù)測靶標。迄今,尚鮮見HIV感染者口腔代謝物分布特征與免疫學(xué)重要指標CD4計數(shù)水平關(guān)系的研究,本研究擬使用GC-TOF-MS檢測平臺,對云南地區(qū)部分HIV感染者口腔液代謝物進行檢測,并分析其與CD4變化關(guān)系,以期發(fā)現(xiàn)與HIV感染疾病進程有關(guān)的新的標志物。[方法]選取2016年9月至2016年12月到昆明市第三人民醫(yī)院感染一科就診且尚未接受高效抗逆轉(zhuǎn)錄病毒治療(HAART)的HIV感染者為病例組,收集受試者的基本信息和口腔液樣本,并記錄CD4計數(shù)�？谇灰簶吮静捎肎C-TOF-MS進行非靶標代謝組學(xué)檢測,對所得數(shù)據(jù)進行預(yù)處理,然后用主成分分析(PCA)、正交偏最小二乘法-判別分析(OPLS-DA)、代謝物定性及差異代謝物篩選、代謝通路分析和層次聚類分析等方法,比較不同CD4水平的HIV感染者之間口腔代謝物變化。[結(jié)果]本研究共收集到90例HIV感染者的口腔液標本90份,按外周血CD4計數(shù)水平分為A組(CD4計數(shù)200個/mm3)、B組(CD4計數(shù)200-500個/mm3)和C組(CD4計數(shù)500個/mm3),每組各30例。所獲標本經(jīng)GC-TOF-MS檢測及生物信息學(xué)分析,主要結(jié)果如下:(1) PCA分析結(jié)果可看出:A組和B組及A組和C組的不同樣品之間大多排列緊湊、聚合成簇,顯示出實驗較好的重復(fù)性,B組和C組的不同樣品之間大多排列比較分散,未能準確的顯示出實驗較好的重復(fù)性;不同實驗分組A組和B組之間,A組和C組之間則互相分離,可以做出清晰的劃分,顯示出不錯的特異性,不同實驗分組B組和C組的樣本出現(xiàn)交疊現(xiàn)象,表明部分樣本間相似度較高,差異性較小。(2) OPLS-DA分析結(jié)果可看出:A和B兩組樣本及A和C兩組樣本互相分離,可以做出清晰的劃分,可以說兩組樣本區(qū)分非常顯著,樣本基本全部處于95%置信區(qū)間內(nèi),表明此數(shù)據(jù)值得進一步研究。而B和C兩組樣本區(qū)分不是非常顯著,但是可以做出劃分,樣本基本全部處于95%置信區(qū)間內(nèi),表明此數(shù)據(jù)也值得進一步研究。(3)代謝物定性及差異代謝物篩選、代謝通路分析和層次聚類分析結(jié)果可看出:A組和B組篩選出來的差異代謝物共116種,差異代謝物映射的KEGG通路7條,其中,最主要的差異代謝通路分別是半乳糖代謝,磷酸戊糖,嘧啶代謝、亞油酸代謝、果糖和甘露糖代謝。A組和C組篩選出來的差異代謝物為133種,差異代謝物映射的KEGG通路9條,其中,最主要的差異代謝通路分別是半乳糖代謝、磷酸戊糖、嘌吟代謝、嘧啶代謝、亞油酸代謝、果糖和甘露糖代謝。B組和C組篩選出來的差異代謝物相對較少,共34種,差異代謝物映射的KEGG通路4條,主要的代謝通路分別是半乳糖代謝、果糖和甘露糖代謝和嘌呤代謝。[結(jié)論]本研究應(yīng)用先進的GC-TOF-MS檢測平臺,分析了外周血不同CD4計數(shù)水平的HIV感染者口腔代謝物的變化特征。研究發(fā)現(xiàn),CD4計數(shù)水平不同,患者口腔內(nèi)代謝差異明顯程度也不同。研究成果可以為發(fā)現(xiàn)HIV感染者新的標志物及疾病控制提供了新的科學(xué)依據(jù)。
[Abstract]:[Objective] changes in oral metabolites can be used in the diagnosis of disease status and / or treatment tolerance. Therefore, the analysis of oral metabolites is helpful for the detection of the target of the HIV disease process. So far, the study of the relationship between the distribution characteristics of oral metabolites and the level of the important immunological index of CD4 counts in HIV infected people. This study is to be used in this study. GC-TOF-MS detection platform was used to detect the oral liquid metabolites of some HIV infected people in Yunnan, and analyze the relationship between them and CD4, in order to find new markers related to the process of HIV infection. [Methods] select the third people's Hospital from September 2016 to December 2016 to be infected with one family and have not received high efficiency antiretroviral The patients with HIV infection (HAART) were the case group. The basic information and oral liquid samples were collected and the CD4 counts were recorded. The oral liquid specimens were detected by GC-TOF-MS for non target metabolism, preprocessed the data, and then used principal component analysis (PCA), orthogonal partial least square method discriminant analysis (OPLS-DA) and metabolite. Sexual and differential metabolites screening, metabolic pathway analysis and hierarchical cluster analysis were used to compare the changes in oral metabolites between HIV infected persons at different CD4 levels. [results] 90 specimens of oral liquid were collected from 90 cases of HIV infection, and were divided into A group (CD4 count 200 /mm3) and B group (CD4 count 200-500 /mm3) according to the CD4 count level of peripheral blood. And group C (CD4 count 500 /mm3), 30 cases in each group. The samples were detected by GC-TOF-MS and bioinformatics analysis. The main results were as follows: (1) the results of PCA analysis showed that the different samples between A and B groups and A and C groups were mostly arranged and clustered, showing good reproducibility, most of the different samples between B and C groups The arrangement of the A group and the B group, the A group and the C group, separated each other, can make a clear division and show the good specificity. The samples of the B and C groups in the different experimental groups appear to overlap, indicating that the similarity of some samples is higher and the difference is more different. (2) (2) the results of OPLS-DA analysis show that two samples of A and B and two groups of A and C can be separated from each other and can make a clear division. It can be said that the two groups of samples are very distinct, and the sample is basically in the 95% confidence interval, indicating that this data is worth further study. And the distinction between the B and the C two groups is not very significant, but can be made. The sample was basically in the 95% confidence interval, indicating that this data was also worthy of further study. (3) the metabolite qualitative and differential metabolite screening, metabolic pathway analysis and hierarchical cluster analysis can be seen: A and B groups of different metabolites selected 116 species, differential metabolite mapping of the KEGG pathway 7, among them, the most important The differential metabolic pathways were galactose metabolism, pentose phosphate, pyrimidine metabolism, linoleic acid metabolism,.A group and C group of fructose and mannose metabolism, 133 different metabolites, and 9 KEGG pathway of differential metabolite mapping, among which the main differential metabolic pathways were galactose metabolism, pentose phosphate, purinyin metabolism, pyrimidine generation. Metabolites of linoleic acid, linoleic acid, fructose and mannose metabolized in group.B and C group were relatively few, 34 species, 4 KEGG pathways of differential metabolite mapping, the main metabolic pathways were galactose metabolism, fructose and mannose metabolism and purine metabolism. [Conclusion] this study applied advanced GC-TOF-MS detection platform and analyzed outside The changes in oral metabolites of HIV infected people with different CD4 counting levels in the peripheral blood have been found to be different in different levels of CD4 count, and the research results can provide new scientific evidence for the discovery of new markers and disease control of HIV infected people.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R512.91
本文編號：2160693
[Abstract]:[Objective] changes in oral metabolites can be used in the diagnosis of disease status and / or treatment tolerance. Therefore, the analysis of oral metabolites is helpful for the detection of the target of the HIV disease process. So far, the study of the relationship between the distribution characteristics of oral metabolites and the level of the important immunological index of CD4 counts in HIV infected people. This study is to be used in this study. GC-TOF-MS detection platform was used to detect the oral liquid metabolites of some HIV infected people in Yunnan, and analyze the relationship between them and CD4, in order to find new markers related to the process of HIV infection. [Methods] select the third people's Hospital from September 2016 to December 2016 to be infected with one family and have not received high efficiency antiretroviral The patients with HIV infection (HAART) were the case group. The basic information and oral liquid samples were collected and the CD4 counts were recorded. The oral liquid specimens were detected by GC-TOF-MS for non target metabolism, preprocessed the data, and then used principal component analysis (PCA), orthogonal partial least square method discriminant analysis (OPLS-DA) and metabolite. Sexual and differential metabolites screening, metabolic pathway analysis and hierarchical cluster analysis were used to compare the changes in oral metabolites between HIV infected persons at different CD4 levels. [results] 90 specimens of oral liquid were collected from 90 cases of HIV infection, and were divided into A group (CD4 count 200 /mm3) and B group (CD4 count 200-500 /mm3) according to the CD4 count level of peripheral blood. And group C (CD4 count 500 /mm3), 30 cases in each group. The samples were detected by GC-TOF-MS and bioinformatics analysis. The main results were as follows: (1) the results of PCA analysis showed that the different samples between A and B groups and A and C groups were mostly arranged and clustered, showing good reproducibility, most of the different samples between B and C groups The arrangement of the A group and the B group, the A group and the C group, separated each other, can make a clear division and show the good specificity. The samples of the B and C groups in the different experimental groups appear to overlap, indicating that the similarity of some samples is higher and the difference is more different. (2) (2) the results of OPLS-DA analysis show that two samples of A and B and two groups of A and C can be separated from each other and can make a clear division. It can be said that the two groups of samples are very distinct, and the sample is basically in the 95% confidence interval, indicating that this data is worth further study. And the distinction between the B and the C two groups is not very significant, but can be made. The sample was basically in the 95% confidence interval, indicating that this data was also worthy of further study. (3) the metabolite qualitative and differential metabolite screening, metabolic pathway analysis and hierarchical cluster analysis can be seen: A and B groups of different metabolites selected 116 species, differential metabolite mapping of the KEGG pathway 7, among them, the most important The differential metabolic pathways were galactose metabolism, pentose phosphate, pyrimidine metabolism, linoleic acid metabolism,.A group and C group of fructose and mannose metabolism, 133 different metabolites, and 9 KEGG pathway of differential metabolite mapping, among which the main differential metabolic pathways were galactose metabolism, pentose phosphate, purinyin metabolism, pyrimidine generation. Metabolites of linoleic acid, linoleic acid, fructose and mannose metabolized in group.B and C group were relatively few, 34 species, 4 KEGG pathways of differential metabolite mapping, the main metabolic pathways were galactose metabolism, fructose and mannose metabolism and purine metabolism. [Conclusion] this study applied advanced GC-TOF-MS detection platform and analyzed outside The changes in oral metabolites of HIV infected people with different CD4 counting levels in the peripheral blood have been found to be different in different levels of CD4 count, and the research results can provide new scientific evidence for the discovery of new markers and disease control of HIV infected people.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R512.91
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