What is Metabolomics?

Metabolomics (metabonomics / metabolomics) is a research method that imitates the research ideas of genomics and proteomics, quantitatively analyzes all metabolites in the body, and finds the relative relationship between metabolites and physiopathological changes component. Its research objects are mostly small molecular substances with a relative molecular mass of less than 1,000. Advanced analysis and detection techniques combined with computational analysis methods such as pattern recognition and expert systems are the basic methods for metabolomics research.

Chinese name: Metabolomics
Foreign name: metabonomics
Imitate: Genomics and Proteomics Research Ideas

Analysis: All metabolites in the body
Belongs to: Systems biology
Research Method: Relative relationship between metabolites and physiopathological changes

Classification of Metabolomics

Metabolomics is a newly developed discipline after genomics and proteomics, and is an important part of systems biology. Since then, it has developed rapidly and penetrated into many fields, such as disease diagnosis, pharmaceutical research and development, nutritional food science, toxicology, environmental science, and botany, which are closely related to human health care. Genomics and proteomics explore the activities of life from the gene and protein levels respectively. In fact, many life activities in cells occur at the metabolite level, such as cell signaling, energy transfer, and intercellular communication Is regulated by metabolites. Metabolomics is just a discipline that studies the metabolome, a collection of all metabolites in a cell at a time. Genes and proteins are closely linked, while metabolites more closely reflect the environment in which the cells are located. This is closely related to the nutritional status of cells, the role of drugs and environmental pollutants, and the impact of other external factors. So some people think, "Genomics and proteomics tell you what might happen, and metabolomics tells you exactly what happened." (Bill Lasley, UC Davis)

The concept of metabolomics is derived from metabolomics. Metabolomics refer to all low molecular weight metabolites of a certain organism or cell in a specific physiological period. Metabolomics refers to all the low molecular weight metabolites of a certain organism or cell in a specific physiological period. A new discipline for qualitative and quantitative analysis of low molecular weight metabolites (Goodacre, 2004). It is a branch of systems biology based on group index analysis, high-throughput detection and data processing, and information modeling and system integration.

The concept that indliduals might have a "metabolic profile" that could be reflected in the makeup of their biological fluids was introduced by Roger Williams in the late 1940s, who used paper chromatography to suggest characteristic metabolic patterns in urine and saliva were associated with diseases such asschizophrenia. However, it was only through technological advancements in the 1960s and 1970s that it became feasible to quantitatively (as opposed to qualitatively) measure metabolic profiles. The term "metabolic profile" was introduced by Horning, et al. in 1971 after they demonstrated that gas chromatography-mass spectrometry (GC-MS) could be used to measure compounds present in human urine and tissue extracts. The Horning group, along with that of Linus Pauling and Arthur B. Robinson led the development of GC-MS methods to monitor the metabolites present in urine through the 1970s.

Gates, Sweeley; Sweeley, CC (1978). "Quantitative metabolic profiling based on gas chromatography". Clin Chem 24 (10): 166373. PMID 359193.

Preti, George. "Metabolomics comes of age?" The Scientist , 19 [11]: 8, June 6, 2005.

Jump up ^ Novotny et al . ; Soini, Helena A .; Mechref, Yehia (2008). "Biochemical indliduality reflected in chromatographic, electrophoretic and mass-spectrometric profiles". J Chromatog B 866 : 2647. Doi: 10.1016 / j .jchromb.2007.10.007.

Jump up ^ Griffiths WJ, Wang Y. (2009). "Mass spectrometry: From proteomics to metabolomics and lipidomics". Chem Soc Rev 38 (7): 188296. Doi: 10.1039 / b618553n.PMID 19551169.

Metabolomics research scope

Metabolomics mainly studies small molecule metabolites (MW <1000) as substrates and products of various metabolic pathways. In the field of food safety, the use of metabolomics tools to discover related biomarkers such as agricultural and veterinary drugs in animals and plants is also a hot area. The samples are mainly extracts of cells and tissues of plants and animals. The main technical means are nuclear magnetic resonance (NMR), mass spectrometry (MS), chromatography (HPLC, GC) and chromatography-mass spectrometry. By detecting the NMR spectrum of a series of samples, combined with pattern recognition methods, the pathophysiological status of the born object can be judged, and it is possible to find out the biomarker related to it. Provide a predictive platform for related early warning signals.

History of Metabolomics

The emergence of metabolomics is a necessity of life science research. Metabolomics, developed in the mid-1990s, is a new discipline for the qualitative and quantitative analysis of small molecule metabolites with a relative molecular weight of less than 1,000 in an organism or cell. As an important part of systems biology, the metabolome has a broad application prospect in the field of clinical medicine.

Metabolites are the final products of gene expression and are produced under the action of metabolic enzymes. Although metabolites are smaller compared to genes or proteins, cells that cannot form metabolites are dead cells, so the importance of metabolites cannot be underestimated.

Researchers can determine whether the body is in a normal state through in-depth research on the body's metabolites, but studies on genes and proteins cannot reach such conclusions. In fact, metabolomics studies have been able to diagnose some metabolic diseases such as diabetes, obesity, and metabolic syndrome. At present, common metabolic pathways that have been clearly studied include the tricarboxylic acid cycle (TCA), glycolysis, and the arachidonic acid (AA) / inflammatory pathway.

Metabolomics research methods

Metabolomic research is similar to proteomics, and there are usually two approaches. One method, called metabolic fingerprinting, uses liquid chromatography-mass spectrometry (LC-MS) to compare individual metabolites in different blood samples to determine all of them. In essence, metabolic fingerprint analysis involves comparing mass spectral peaks of metabolites in different individuals, finally understanding the structure of different compounds, and establishing a comprehensive set of analytical methods to identify the characteristics of these different compounds. Another method is metabolic profiling, in which researchers hypothesize a specific metabolic pathway and investigate it further.

For metabolites, it is not just the mass spectral peak. Furthermore, mass spectrometry (MS) cannot detect all metabolites, not because the mass spectrometry is not sensitive enough, but because mass spectrometry can only detect ionized substances, but some metabolites cannot be ionized in a mass spectrometer. The use of nuclear magnetic resonance (NMR) method can make up for the lack of chromatography. Dr Jules Griffin of the University of Cambridge is using a combination of mass spectrometry and nuclear magnetic resonance to try to build a complete map of metabolic pathways in the body. Griffin uses nuclear magnetic resonance to detect high-abundance metabolites. Because the sensitivity of NMR detection is not high, it is only used to analyze low-abundance metabolites.

In the past, only toxicology studies used nuclear magnetic resonance, while mass spectrometry was used only in plant metabolism studies. These two methods are now commonly used in metabolomics research. To make meaningful comparisons between different samples, researchers must combine the vast amounts of data obtained from both methods for analysis. In addition, data from genomics studies need to be combined.

Dr. Gary Siuzdak is engaged in bioinformatics research at the Clippers Research Institute (TSRI) in the United States. He has designed an experimental protocol for analyzing changes in metabolites from different samples. Researchers can compare different data with the bioinformatics software XEMS to identify metabolites. The software provides molecular weight data for all metabolites whose concentrations vary from individual to individual. This data is freely available to the public online.

Dr. Siuzdak said that they are using comprehensive research methods for metabolomics research, trying to detect as many metabolites as possible, exceeding the goals that people can use in the past. Through individual research, I hope that to a certain extent, new molecules related to stress can be identified. These stressors may be a disease, a knock-out enzyme, or other substances.

Development Prospects of Metabolomics

Better "omics"?

Metabolomics is an emerging "omics" following genomics, proteomics, and transcriptomics. Since 1999, the number of metabolomics research articles published each year has been increasing. On the surface, metabolomics has developed rapidly, but it still lags far behind genomics and proteomics. "We are still looking forward to major discoveries," explains Dr. Griffin, and those articles published in Nature have made people look forward to metabolomics: finding a new biomarker, discovering a new metabolic pathway, or Learn more about these approaches currently known.

Although no classic papers have appeared, researchers believe that metabolomics will play a greater clinical role than genomics and proteomics. Many companies have found through market research that healthy people do not want genotyping, so for these populations, genomics research has limited clinical applications. Metabolomics is similar to clinical chemistry, and provides less personal information than genomics, so its clinical application may have some impact. Lower cost is another reason that makes metabolomics clinically acceptable. Dr. Griffin pointed out that compared to other "omics" studies, metabolomics is less expensive, and researchers can use metabolomics research to screen for metabolites and then use more expensive genomics and proteomics methods Significant metabolites are further investigated. First, metabolites must be identified. This is not a simple task. According to Dr. Siuzak, the biggest challenge in metabolomics research is the identification of metabolites, which is also the most interesting aspect, and the more challenging work is to further confirm the function of all metabolites. In addition, mass spectrometry analysis found that the homogeneity of the metabolites was not high. Due to the lack of homogeneity, chromatographic analysis became more difficult, and unknown substances in the samples could not be identified.

Metabolomics diagnosis

Compared with genomics and proteomics, metabolomics research focuses on the commonality of related specific components, and ultimately involves the study of the commonalities, characteristics, and laws of each metabolic component. At present, the goals are far away. Despite the challenges, researchers remain convinced that metabolomics is more closely related to physiology than genomics and proteomics. Diseases cause changes in the pathophysiological processes of the body, and eventually cause corresponding changes in metabolites. By analyzing certain metabolites and comparing them with normal people's metabolites, looking for biomarkers of disease will provide a better disease diagnosis method.

Metabolomics Medical Applications

Metabolomics researchers have studied this. Whether a newborn is missing an enzyme gene can be detected at birth. Detects enzymes that include essential components (such as amino acids) in synthetic pathways. As a result of the enzyme deficiency, the corresponding metabolite is too little or too much. Phenylketonuria (PKU) is a common infant disease. This disease is caused by the absence of the phenylalanine hydrolase gene necessary for the hydrolysis of phenylalanine to tyrosine, which results in the accumulation of phenylalanine in the blood. Failure to detect this natural metabolic deficiency in a timely manner can cause irreparable brain damage within nine months of the baby's birth. The disease can be diagnosed with a simple blood sample and urea test. Blood samples and urea tests will also become part of the research methods of metabolic fingerprinting. For diseases like phenylketonuria, researchers are trying to start with the biochemical basis of the disease, rather than just detecting biomarkers. They hope that through metabolomics, they can find better ways to treat these diseases.

Testimonials from Metabolomics Experts

Dr. Siuzdak is optimistic and realistic about metabolomics. "Metabolomics is still in its infancy," he explained. If we can understand 5 to 10% of metabolites, we are lucky. If this is considered, the reality is that we still know nothing about the role of these molecules. However, it is believed that with the continuous improvement and optimization of its methods, metabolomics research will surely become a powerful means for humans to diagnose diseases more efficiently and accurately.