代谢组学详细

代谢组学 > 代谢组学

    代谢组学

     


            代谢组学
    (Metabolomics)的概念最早由英国   Nicholson于1999年提出,是系统生物学的有机组成部分。代谢组学旨在对生物体内所有代谢物进行定量分析,并寻找代谢物与生理病理变化的相对关系。代谢组学的研究对象大都是相对分子质量小于1000小分子物质,它们参与到生物体的新陈代谢和生长发育的方方面面,是生物现象的最终产物。


    QQ图片20160310142556.png


            相比基因组和蛋白组的研究,代谢组学研究具有独特的应用优势:1. 基因和蛋白表达的微小变化可通过代谢酶的催化反应在代谢物上得以放大,从而使检测和分析更加容易;2. 代谢物的变化除了反应基因组变化外,还受到环境因素、肠道菌群的影响,其动态性更强,对生物体变化的反映更加灵敏(如上图);3. 代谢反应及终产物在各个物种的生物体系中都是类似的,因此,代谢组学方法学通用性更强;4. 代谢组学的技术不需建立全基因组测序及大量表达序列数据库,直接对几乎所有样本类型进行检测,包括全血、血浆/血清、组织、细胞、细胞培养上清、尿液、粪便、食物、唾液、脑脊液、脂肪等。

         
            经过近20年的发展,代谢组学的研究技术手段逐步成熟。目前质谱技术:气质联用技术(GC-MS)和液质联用技术(LC-MS),已逐步取代核磁技术(NMR),成为代谢组学研究的主流技术。GC-MS和LC-MS在其所检测的代谢物谱上各有偏向性(如下图),一般情况两种技术联合使用是常规全谱代谢组分析的主要实验策略。

     

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    技术路线:

     


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    样品要求:



            代谢组的差异变化是基因组变化放大效应的呈现,不同个体中代谢物的波动性也就较大。另一方面,代谢组学的差异分析一般是基于PCA和PLS-DA等多元统计分析方法进行的,只有较大的样本量抽提出的主成分才具有群体代表性。因此,相对于基因组学等技术方法,代谢组学要求样品的生物学重复要更多。

                           1.细胞样品大于6例

                           2.临床标本大于30例
                           3.模式动物样品大于10例
                           4.植物微生物样品每组大于8例



    应用方向:



                             1.疾病标志物开发        
                             2.肿瘤/癌症        
                             3.代谢疾病/心血管疾病       
                             4.营养学        
                             5.炎症/免疫         
                             6.感染性疾病        
                             7.神经科学        
                             8.植物学        
                             9.药物开发        
                             10.毒理研究         
                             11.微生物研究 


    相关文献:


    转录组与代谢组联合分析

    1. He J, Wang K, Zheng N, et al. Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration. Sci Rep-UK, 2015; 5.

    2. Langley R J, Tipper J L, Bruse S, et al. Integrative “omic” analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes. Am J Resp Crit Care, 2014, 190(4): 445-455.

    3. Zhou M, Wang S, Zhao A, et al. Transcriptomic and metabonomic profiling reveal synergistic effects of quercetin and resveratrol supplementation in high fat diet fed mice. J Proteome Res, 2012; 11(10): 4961-4971.

    4. Li H, Xie Z, Lin J, et al. Transcriptomic and metabonomic profiling of obesity-prone and obesity-resistant rats under high fat diet. J Proteome Res, 2008; 7(11): 4775-4783.

       

    疾病标志物研究

    1. Butte N F, Liu Y, Zakeri I F, et al. Global metabolomic profiling targeting childhood obesity in the Hispanic population. Am J Clin Nutr, 2015; ajcn111872.

    2. Barrios C, Beaumont M, Pallister T, et al. Gut-Microbiota-Metabolite Axis in Early Renal Function Decline. PloS one, 2015; 10(8): e0134311.

    3. Mondul A M, Moore S C, Weinstein S J, et al. Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha‐tocolpherol, beta‐carotene cancer prevention (ATBC) study. Int J Cancer, 2015; 137(9): 2124-2132.

    4. Yousri N A, Mook-Kanamori D O, Selim M M E D, et al. A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control. Diabetologia, 2015; 58(8): 1855-1867.

    5. Kurland I J, Broin P Ó, Golden A, et al. Integrative metabolic signatures for hepatic radiation injury. PloS one, 2015; 10(6): e0124795.

       

    肿瘤/癌症研究

    1. Modesitt S C, Hallowell P T, Slack-Davis J K, et al. Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life. Gynecol Oncol, 2015; 138(2): 238-245. 

    2. Ventura R, Mordec K, Waszczuk J, et al. Inhibition of de novo palmitate synthesis by fatty acid synthase induces apoptosis in tumor cells by remodeling cell membranes, inhibiting signaling pathways, and reprogramming gene expression. EBioMedicine, 2015; 2(8): 808-824.

    3. Pan P, Skaer C W, Wang H T, et al. Black raspberries suppress colonic adenoma development in ApcMin/+ mice: relation to metabolite profiles. Carcinogenesis, 2015; 36(10): 1245-1253.

    4. Wettersten H I, Hakimi A A, Morin D, et al. Grade-dependent metabolic reprogramming in kidney cancer revealed by combined proteomics and metabolomics analysis. Cancer Res, 2015; 75(12): 2541-2552.

    5. Granata A, Nicoletti R, Perego P, et al. Global metabolic profile identifies choline kinase alpha as a key regulator of glutathione-dependent antioxidant cell defense in ovarian carcinoma. Oncotarget, 2015; 6(13): 11216.


    代谢疾病/心血管疾病

    1. Modesitt S C, Hallowell P T, Slack-Davis J K, et al. Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life. Gynecol Oncol, 2015; 138(2): 238-245. 

    2. Li Q, Freeman L M, Rush J E, et al. Veterinary medicine and multi-omics research for future nutrition targets: Metabolomics and transcriptomics of the common degenerative mitral valve disease in dogs. Omics, 2015; 19(8): 461-470

    3. Shirai M, Matsuoka M, Makino T, et al. Hepatic glutathione contributes to attenuation of thioacetamide-induced hepatic necrosis due to suppression of oxidative stress in diet-induced obese mice. J Toxicol Sci, 2015; 40(4): 509-521.

    4. Menghini R, Casagrande V, Cardellini M, et al. FoxO1 regulates asymmetric dimethylarginine via downregulation of dimethylaminohydrolase 1 in human endothelial cells and subjects with atherosclerosis. Atherosclerosis, 2015; 242(1): 230-235.

    5. Guo L, Milburn M V, Ryals J A, et al. Plasma metabolomic profiles enhance precision medicine for volunteers of normal health. PNAS, 2015; 112(35): E4901-E4910.

     

    营养学研究

    1. Li Q, Freeman L M, Rush J E, et al. Veterinary medicine and multi-omics research for future nutrition targets: Metabolomics and transcriptomics of the common degenerative mitral valve disease in dogs. Omics, 2015; 19(8): 461-470.

    2. Prasad G L, Jones B A, Schmidt E, et al. Global metabolomic profiles reveal differences in oxidative stress and inflammation pathways in smokers and moist snuff consumers. J Metabolomics, 2015; 1(1): 2.

    3. Richter C L, Kennedy A D, Guo L, et al. Metabolomic Measurement of Three Timepoints in a Saccharomyces cerevisiae Chardonnay Wine Fermentation. Am J Poentgenol, 2015; ajev. 2015.14062.

    4. Marchesan J T, Morelli T, Moss K, et al. Association of Synergistetes and Cyclodipeptides with Periodontitis. J Dent Res, 2015; 0022034515594779.

    5. Beltrán-Debón R, Rodríguez-Gallego E, Fernández-Arroyo S, et al. The acute impact of polyphenols from Hibiscus sabdariffa in metabolic homeostasis: an approach combining metabolomics and gene-expression analyses. Food & Function, 2015; 6(9): 2957-2966.


    药理/毒理

    1. Okamoto H, Kim J, Aglione J P, et al. Glucagon Receptor Blockade With a Human Antibody Normalizes Blood Glucose in Diabetic Mice and Monkeys. Endocrinology, 2015; 156(8): 2781-2794.

    2. Zhao Y, Hu Q, Cheng F, et al. SoNar, a Highly Responsive NAD+/NADH Sensor, Allows High-Throughput Metabolic Screening of Anti-tumor Agents. Cell Metab, 2015; 21(5): 777-789.

    3. Shirai M, Matsuoka M, Makino T, et al. Hepatic glutathione contributes to attenuation of thioacetamide-induced hepatic necrosis due to suppression of oxidative stress in diet-induced obese mice. J Toxicol Sci, 2015; 40(4): 509-521.

    4. Miller D B, Karoly E D, Jones J C, et al. Inhaled ozone (O 3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats.Toxicol Appl Pharm, 2015; 286(2): 65-79.

    5. Zhao Z, Van Oort A, Tao Z, et al. Metabolite profiling of 5′-AMP induced hypometabolism. Metabolomics, 2014; 10(1): 63-76.


    炎症/免疫/感染

    1. Greineisen W E, Maaetoft-Udsen K, Speck M, et al. Chronic Insulin Exposure Induces ER Stress and Lipid Body Accumulation in Mast Cells at the Expense of Their Secretory Degranulation Response. PloS one, 2015; 10(8): e0130198.

    2. Tarasenko T N, Singh L N, Chatterji-Len M, et al. Kupffer cells modulate hepatic fatty acid oxidation during infection with PR8 influenza. BBA-Mol Basis Dis, 2015; 1852(11): 2391-2401.

    3. Patsoukis N, Bardhan K, Chatterjee P, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun, 2015; 6.

    4. Gerriets V A, Kishton R J, Nichols A G, et al. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest, 2015; 125(1): 194.

    5. Chuang Y M, Bandyopadhyay N, Rifat D, et al. Deficiency of the novel exopolyphosphatase Rv1026/PPX2 leads to metabolic downshift and altered cell wall permeability in Mycobacterium tuberculosis. MBio, 2015; 6(2): e02428-14.


    植物学/微生物学

    1. Rabara R C, Tripathi P, Reese R N, et al. Tobacco drought stress responses reveal new targets for Solanaceae crop improvement. BMC Genomics, 2015; 16(1): 1. 

    2. Tuttle J R, Nah G, Duke M V, et al. Metabolomic and transcriptomic insights into how cotton fiber transitions to secondary wall synthesis, represses lignification, and prolongs elongatio. BMC Genomics, 2015; 16(1): 1.

    3. Rudd J J, Kanyuka K, Hassani-Pak K, et al. Transcriptome and metabolite profiling of the infection cycle of Zymoseptoria tritici on wheat reveals a biphasic interaction with plant immunity involving differential pathogen chromosomal contributions and a variation on the hemibiotrophic lifestyle definition. Plant Physiol, 2015; 167(3): 1158-1185.

    4. Marchesan J T, Morelli T, Moss K, et al. Association of Synergistetes and Cyclodipeptides with Periodontitis. J Dent Res, 2015; 0022034515594779.

    5. He B, Nohara K, Ajami N J, et al. Transmissible microbial and metabolomic remodeling by soluble dietary fiber improves metabolic homeostasis. Sci Rep-UK, 2015; 5.