代谢组学能干什么？

“我的同事Ron Morrison曾经认真地问我什么是代谢组，如何采用代谢组学进行合作研究。他是研究胰岛素信号转导MAPK通路中的ERK 和JNK途径的，我问他知道跟肥胖表型相关的一共有多少个基因多少条通  路？他所研究的JNK途径对于一个肥胖表型的发生大致贡献率是多大    呢？他摇摇头说这些都说不好。我说打个比方，从我们校园到Greensboro的飞机场理论上有无数条途径可走，但你我都知道比较可行的途径也就是少数两三条。现在的问题是都不知道这2－3条最重要的通路时，我们各自在自己熟悉的道路上潜心研究，都发现了有通往机场的车流量经过你的Market Street和我的Spring Garden Street，都认为自己研究的可能就是那主要的2－3条道之一，十年以后也许我们认识到我们都错了。现在我们有一种技术对交通的正常状况、繁忙状况和瘫痪状况进行航    拍，通过比较发现当XYZ共3条道路阻塞以后前往机场的交通才真正瘫痪，那么我们就可以有针对性地研究这几条道路    了。代谢组学就是这种“航拍”技术，它不做任何假设，针对疾病和健康两种状态（人群）进行代谢物全谱检测，帮你寻找出与疾病相关的一组差异物，可能会有好几十个，从它们所在的被上调或下调的代谢通路上我们再去找到关键的代谢（限速）酶，再找到它们上游的调控基因。代谢组学有很多功能，如生物标志物的发现，疾病早期诊断和预测，药物或营养干预的评价，药物毒性评价，代谢工程研究，等等，但它也仅仅是个平台技术，不是万能的，无法独立开展机制性研究；而用代谢组学与分子生物学协同研究，进行“导航”，就可以起到事半功倍的作用。”——摘自贾伟博客

代谢组学的应用：代谢组学技术已广泛应用于生物学和医学相关的各个领域，如疾病诊断，发病机制研究，中医药现代化，药物毒理及安全评价，植物，微生物，环境、营养等研究。

代谢组学应用实例解析一：大麦盐胁迫GC-MS代谢组学研究

浙江大学农学系张国平教授课题组采用GC-MS代谢组学技术对大麦野生型及栽培型盐胁迫响应差异进行分析，发现渗透调节是抗盐作用的基础机制。根中高水平的糖和能量以及叶中光合作用的促进反应对大麦抗盐起到重要作用，另外发现多元醇只在根的抗盐作用中扮演重要角色。该成果于2013年1月发表在国际期刊PLOS ONE上，目前已被引用8次，成为代谢组学技术在植物胁迫作用研究中应用的典范。

实验设计：
大麦样本48个，包括两个品种（A品种和B品种）、两种组织（根和叶）和两种生长条件（正常与盐处理），每组样本含6个重复。

品  种	组织类型	生长条件	样本数量	分  类
XZ16品种	叶片	正常	6	XZ16-CK
XZ16品种	根	正常	6	XZ16-CK
CM72品种	叶片	正常	6	CM72-CK
CM72品种	根	正常	6	CM72-CK
XZ16品种	叶片	盐处理	6	XZ16-T
XZ16品种	根	盐处理	6	XZ16-T
CM72品种	叶片	盐处理	6	CM72-T
CM72品种	根	盐处理	6	CM72-T

研究结果：

CM72和XZ16两品种的根、叶的对照组和高浓度组的代谢组学PCA得分图。(A)根的PCA得分图；（B）叶的PCA得分图；CK：对照组；T：盐处理组；PC1：第一主成分；PC2：第二主成分。
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原文摘要：
Abstract
A thorough understanding of the mechanisms underlying barley salt tolerance and exploitation of elite genetic

resource are essential for utilizing wild barley germplasm in developing barley varieties with salt tolerance. In

order to reveal the physiological and molecular difference in salt tolerance between Tibetan wild barley (Hordeum

spontaneum) and cultivated barley (Hordeum vulgare), profiles of 82 key metabolites were studies in wild and

cultivated barley in response to salinity. According to shoot dry biomass under salt stress, XZ16 is a fast growing

and salt tolerant wild barley. The results of metabolite profiling analysis suggested osmotic adjustment was a

basic mechanism, and polyols played important roles in developing salt tolerance only in roots, and high level of

sugars and energy in roots and active photosynthesis in leaves were important for barley to develop salt

tolerance. The metabolites involved in tolerance enhancement differed between roots and shoots, and also

between genotypes. Tibetan wild barley, XZ16 had higher chlorophyll content and higher contents of compatible

solutes than CM72, while the cultivated barley, CM72 probably enhanced its salt tolerance mainly through

increasing glycolysis and energy consumption, when the plants were exposed to high salinity. The current

research extends our understanding of the mechanisms involved in barley salt tolerance and provides possible

utilization of Tibetan wild barley in developing barley cultivars with salt tolerance.

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代谢组学应用实例解析二：二型糖尿病LC-MS代谢组学研究

黑龙江中医药大学王喜军教授课题组采用UPLC-Q-TOF-MS技术对二型糖尿病及正常人群尿液样品进行代谢组学分析，发现的一些biomarkers为脂连素，酰基肉毒碱，柠檬酸，犬尿烯酸，3-吲哚酚硫酸盐以及葡萄糖等化合物，这些化合物作用的几个关键代谢通路为牛磺酸及亚牛磺酸代谢，半胱氨酸及甲硫氨酸代谢，缬氨酸，亮氨酸及异亮氨酸生物合成代谢等通路。该成果发表在J Physiol Biochem上，再一次证明了代谢组学在临床早期诊断以及疾病发病机制的研究中具有巨大潜力及广阔的发展空间。

实验设计：
人尿液样品80例，其中二型糖尿病40例，正常对照40例。

物种	样品类型	分组	样本数量
Human	Urine	T2D	40
Human	Urine	C	40

研究结果：

二型糖尿病LC-MS代谢组学多元变量统计分析，a 尿液代谢PCA二维得分图；b 尿液代谢PCA三维得分图；c PLS-DA模型化合物VIP散点图。

原文摘要：
Abstract

Type 2 diabetes (T2D), called the burden of the twenty-first century, is growing with an epidemic rate. Here, we

explored the differences in metabolite concentrations between T2D patients and healthy volunteers.

Metabolomics represents an emerging discipline concerned with comprehensive analysis of small molecule

metabolites and provides a powerful approach to discover biomarkers in biological systems. The acquired data

were analyzed by ultra-performance liquid chromatography–electrospray ionization/quadrupole time-of flight high-

definition mass spectrometry coupled with pattern recognition approach [principal component analysis(PCA) and

partial least squares discriminant analysis(PLS-DA) to identify potential disease-specific biomarkers. PCA

showed satisfactory clustering between patients and healthy volunteers. Biomarkers reflected the biochemical

events associated with early stages of T2D which were observed in PLS-DA loading plots. These urinary

differential metabolites, such as adiponectin, acylcarnitines, citric acid, kynurenic acid, 3-indoxyl sulfate, urate, and

glucose, were identified involving several key metabolic pathways such as taurine and hypotaurine metabolism;

cysteine and methionine metabolism; valine, leucine, and isoleucine biosynthesis metabolism, etc.Our data

suggest that robust metabolomics has the potential as a noninvasive strategy to evaluate the early

diagnosis of T2D patients and provides new insight into pathophysiologic mechanisms and may enhance the

understanding of its cause of disease.

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