Historically, the suffix -omics has been used to describe something big or important, but in the world of life science, it has taken on even greater meaning. In this post, I would like to discuss how it became a popular buzz word used to describe large-scale data that tells a story and ultimately explains life. And, as an former analytical chemist, discuss the role of gas chromatography-mass spectrometry (GC-MS) in metabolomics analysis, which, according to the Metabolomics Society website, is to provide “comprehensive characterization of small molecule metabolites in biological systems.”
Genomics, Proteomics, and Metabolomics: The Big 3 OMICS
As mentioned above, -omics can refer to myriad things but the Big Three are genomics, proteomics, and metabolomics. Genomics is the study of the genetic make-up of organisms and proteomics is the study of proteins and how their structure allows them to do what they do. Together, genomics and proteomics provide extensive information about the genotype of an organism, but they convey limited information about phenotype.
The third of the Big Three, metabolomics, provides the best link between genotype and phenotype, with its focus on the complete set of low-molecular-weight compounds in a sample. These compounds are the substrates and by-products of enzymatic reactions and have a direct effect on the phenotype of the cell. The goal of metabolomics is to understand the profile of all of these compounds at specified times, under specific environmental conditions, ultimately helping understand how the metabolism in an organism leads to phenotype.
Why Metabolomics Analysis Has Lagged behind Proteomics
Proteomics research has been propelled by complex software and statistical packages but it has been challenging to develop the right instruments and software packages for metabolomics, and consequently, metabolomics research has lagged somewhat behind proteomics studies. Metabolomics was initially investigated using only mass and retention time. Today, metabolomics research is finally catching up, using sophisticated chromatography software packages, such as our Thermo Scientific TraceFinder software to collect robust, quantitative data to identify metabolites. Indeed, such software has become indispensable in the metabolomics community.
Advantages of GC-MS Analysis of Small Molecules
Separation techniques, such as the earlier-mentioned GC-MS, liquid chromatography-mass spectrometry (LC-MS), and capillary electrophoresis mass spectrometry (CEMS), are typically used to achieve comprehensive analysis of small molecules. Liquid chromatography can be used to analyze a wide range of low-to-high polarity metabolites, but does not achieve the excellent resolution possible with the GC technique which provides excellent separation, allowing efficient and precise separation of structurally similar metabolites. In addition, the GC-MS technique offers high resolution by GC and high sensitivity by MS and can be used for analysis of low-polarity volatile metabolites of fats and esters, and high polarity metabolites of amino acids and organic acids converted.
New HRAM GC-MS instruments (such as the Thermo Scientific Q Exactive GC Orbitrap GC-MS/MS system) are changing the way metabolomics research is conducted because they allow for both targeted and untargeted metabolomics (link to downloadable PDF application note). The software allows for automating metabolite identification using enhanced spectral deconvolution, NIST library candidate searching, and accurate mass filtering. The added resolution provided by the Orbitrap MS helps distinguish peaks that might have appeared as one using LC-MS.
In the following 5-min video, Karl Burgess, a metabolomics expert from Glasgow Polyomics, talks about his recent experience using this new system.