Metabolomics Standards Workshop and the development of international standards for reporting metabolomics experimental results

Informatics standards and controlled vocabularies are essentialfor allowing information technology to help exchange, manage,interpret and compare large data collections. In a rapidly evolvingfield, the challenge is to work out how best to describe, butnot prescribe, the use of these technologies and methods. AMetabolomics Standards Workshop was held by the US NationalInstitutes of Health (NIH) to bring together multiple ongoingstandards efforts in metabolomics with the NIH research community.The goals were to discuss metabolomics workflows (methods, technologiesand data treatments) and the needs, challenges and potentialapproaches to developing a Metabolomics Standards Initiativethat will help facilitate this rapidly growing field which hasbeen a focus of the NIH roadmap effort. This report highlightsspecific aspects of what was presented and discussed at the1st and 2nd August 2005 Metabolomics Standards Workshop.      

代谢组学及其应用

对代谢组学的概念、特性、发展历史做了简要介绍,综述了当前代谢组学研究中的数据采集、数据分析中采用的技术,及代谢组学在疾病诊断、药物毒性研究、植物和微生物等邻域的应用,并对代谢组学的发展作了展望。     

Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice

Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) was applied for the analysis of complex metabolite profiles from mouse spleen. The resulting two-dimensional chromatograms proved that mass spectral quality and sensitivity were largely improved by the enhanced resolution and zone compression, which are features of GC × GC operation, when compared to classical one-dimensional GC-TOF methods. The improved peak capacity of GC × GC allowed for peaks to be detected that could previously not be separated in one-dimensional GC. A measure of the combined power of chromatographic and mass spectral deconvolution resolution is called “analytical purity”, with higher values indicating less pure peaks. GC × GC-TOF lead to the detection of 1200 compounds with purity better than 0.2, compared to 500 compounds with purity up to 2.5 in one-dimensional GC-TOF. The compounds identified include many of the compounds previously reported in NMR studies and other methods on mammalian tissues. Spleen samples of several obese NZO mice and lean C57BL/6 control strains were analyzed in order to demonstrate the applicability of GC × GC-TOF for biomarker identification.This revised version was published online in June 2005. The previous version did not contain colour images.     

植物代谢组学研究进展

代谢组学是继基因组学、转录组学和蛋白质组学之后发展起来的一门学科,通过对细胞内的基因表达最终代谢产物的定性和定量分析以及定义细胞或器官的生化表现类型来解释功能基因的表达过程。文中就代谢组学的发展历史、主要研究内容、技术特点、数据处理过程及在植物领域中的应用的最新进展几方面进行阐述,以供读者参考。     

Mass spectrometry methods in metabolomics

The review deals with metabolomics, a new and rapidly growing area directed to the comprehensive analysis of metabolites of biological objects. Metabolites are characterized by various physical and chemical properties, traditionally studied by methods of analytical chemistry focused on certain groups of chemical substances. However, current progress in mass spectrometry has led to formation of rather unified methods, such as metabolic fingerprinting and metabolomic profiling, which allow defining thousands of metabolites in one biological sample and therefore draw “a modern portrait of metabolomics.” This review describes basic characteristics of these methods, ways of metabolite separation, and analysis of metabolites by mass spectrometry. The examples shown in this review, allow to estimate these methods and to compare their advantages and disadvantages. Besides that, we consider the methods, which are of the most frequent use in metabolomics; these include the methods for data processing and the required resources, such as software for mass spectra processing and metabolite search database. In the conclusion, general suggestions for successful metabolomic experiments are given.     

代谢物组学的研究进展

结构基因组学、蛋白质组学和转录物组学的研究产生了大量关于基因表达和蛋白质表达的数据,但同时,它们与功能基因组学的研究相比也显示出了局限性。与之相对,生物体内代谢物组的研究有广阔的前景,这便随之产生了代谢物组学。本系统地综述了代谢物组学的最新发展动态,主要包括代谢物组学的研究内容、研究手段及其应用领域等方面。     

Metabolomics: building on a century of biochemistry to guide human health

Medical diagnosis and treatment efficacy will improve significantly when a more personalized system for health assessment is implemented. This system will require diagnostics that provide sufficiently detailed information about the metabolic status of individuals such that assay results will be able to guide food, drug and lifestyle choices to maintain or improve distinct aspects of health without compromising others. Achieving this goal will use the new science of metabolomics – comprehensive metabolic profiling of individuals linked to the biological understanding of human integrative metabolism. Candidate technologies to accomplish this goal are largely available, yet they have not been brought into practice for this purpose. Metabolomic technologies must be sufficiently rapid, accurate and affordable to be routinely accessible to both healthy and acutely ill individuals. The use of metabolomic data to predict the health trajectories of individuals will require bioinformatic tools and quantitative reference databases. These databases containing metabolite profiles from the population must be built, stored and indexed according to metabolic and health status. Building and annotating these databases with the knowledge to predict how a specific metabolic pattern from an individual can be adjusted with diet, drugs and lifestyle to improve health represents a logical application of the biochemistry knowledge that the life sciences have produced over the past 100 years.     

Evaluation of NMR spectral data of urine in conjunction with measured clinical chemistry and histopathology parameters to assess the effects of liver and kidney toxicants

Single low and high doses of several compounds with known renal toxic effects (para-aminophenol, puromycin aminonucleoside, sodium chromate, and hexachlorobutadiene,) or known liver toxic effects (galactosamine, allyl alcohol, and thioacetamide) were administered to male Wistar rats in groups of 4 or 8 for each compound. Predose urine samples (Day 0) and samples from post-dosing (Days 1–4) were collected for each rat and monitored by 1D ¹H NMR. Principal component analysis (PCA) of the NMR spectra was used to investigate differences between dose levels for each compound individually. The findings from PCA at both dose levels for each compound were examined in the context of the corresponding clinical chemistry and pathology data collected during the study. The PCA clustering of NMR spectra from rats dosed with each individual compound were shown to be associated with the measured levels of creatinine, BUN, AST, ALT and histopathology findings. Finally, scaled-to-maximum, aligned, and reduced trajectories (SMART) analysis was applied to compare the temporal metabolic trajectories obtained for each animal at each dose level of the administered compounds. By day 4, the SMART trajectories for allyl alcohol and hexachlorobutadiene had returned to predose levels indicating a recovery response, however, the high dose SMART trajectories for para-aminophenol, puromycin aminonucleoside, sodium chromate, and galactosamine did not appear to return to predose levels indicating a prolonged toxic effect.     

代谢组学在临床研究中的应用及进展

代谢组学是"后基因组学"时期新兴的一门学科,也是系统生物学的重要组成部分。代谢组学通过全面、定量检测生物样本中多种类型小分子化合物,来了解在内在和外界因素作用下生物体内源性物质的变化及规律,特别适合于临床上研究机体因受到遗传、生长、生理、环境因素和异物、病源等刺激的影响而产生的变化。借助于代谢组学技术不仅能够描述疾病发生、发展以及治疗过程中机体代谢机能的状态和变化,为临床疾病的诊断、病理机制的探索、新治疗靶点的发现等提供新的途径和思路,还可以揭示外界干扰因素(药物/毒物、环境、饮食、生活方式等)对机体的影响,为药效评价和疾病病因的筛查提供基础数据。近年来,代谢组学在临床研究方面得到了广泛的应用,取得了巨大的进展并展现了鼓舞人心的应用前景。该文分别就代谢组学在描述疾病发展状态、研究疾病诊断方法、探索疾病发病原因和发病机理、药效学评价等几个方面的应用及进展进行回顾和综述。     

基因组尺度代谢网络研究进展

基因组尺度代谢网络从基因组序列出发,结合基因、蛋白质、代谢数据库和实验数据,从系统的角度定量研究生命体的代谢过程,了解各个组分之间的相互作用关系。这类网络模型对于生命活动理论研究和优良工程菌的构建都具有重要的理论和实践意义。以下结合作者的实际研究经验,对基因组尺度代谢网络从重构到模拟直至应用进行了较为详细的介绍,并讨论了一些目前存在的难题和未来的研究方向。     

Systems approaches to succinic acid-producing microorganisms

Succinic acid is a cellular metabolite belonging to the C4-dicarboxylic acid family, and the fermentative production of succinic acid via the use of recombinant microorganisms has recently become the focus of an increasing amount of attention. Considering the difficulty inherent to the direct application of natural succinic acid producers to the industrial process, a variety of systems biology studies have been conducted regarding the development of enhanced succinic acid production systems. This review shows how the metabolic processes of microorganisms, includingEscherichia coli andMannheimia succiniciproducens, have been optimized in order to achieve enhanced succinic acid production. First, their metabolic networks were constructed on the basis of complete genome sequences, after which their metabolic characteristics were estimated viain silico computer modeling. Metabolic engineering strategies were designed in accordance with the results ofin silico modeling and metabolically engineered versions of bothE. coli andM. succiniciproducens have been constructed. The succinic acid productivity and yield obtained using metabolically engineered bacteria was significantly higher than that obtained using wild-type bacteria.     

双香豆素抑制SL-221细胞增殖的差异代谢物分析

为明确双香豆素（DIC）对斜纹夜蛾Spodoptera litura卵巢细胞（SL-221）代谢组的影响。本研究采用CCK-8和非靶向代谢组学技术研究双香豆素抑制SL-221细胞增殖的毒理机理。结果表明,双香豆素对SL-221细胞表现出明显的抑制活性,24 h的抑制中浓度为1.60 μg/mL,且呈浓度依赖性;此外,双香豆素分别与SC 79和胰岛素共培养后,均能提升细胞活力;进一步通过非靶向代谢组学技术获得了393个差异代谢物,双香豆素与对照相比上调了364个,下调29个,而50%以上的差异代谢物分布于氨基酸及其代谢物（48.3%）和甘油磷脂类（14.2%）中;差异代谢物富集主要在氨基糖和核苷酸糖的代谢、不饱和脂肪酸的生物合成、糖的生物合成、淀粉和蔗糖等营养代谢途径中;其中,差异代谢产物肾上腺甾酮（Adrenosterone）、LPC(12:0/0:0)、N,N-二环己基碳二亚胺（N,N-dicyclohexylcarbodiimide）和L-缬氨酸-L-脯氨酸（Val-Pro）分别上调了5 833.56倍、15.47倍、10.26倍和9.94倍。本研究解析了双香豆素诱导斜纹夜蛾卵巢细胞增殖的代谢调控机制,为该化合物的开发利用提供了理论依据。     

代谢工程发展20年

代谢工程从上世纪90年代初期发展至今已有20年历史,对微生物发酵工业的发展起到了极大的推动作用。以下回顾了代谢工程发展至今的三个重要阶段,讨论了各阶段中代谢工程在技术方面的进展及其对微生物发酵工业的促进作用。最后还讨论了代谢工程将来发展中的关键问题及解决策略。