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Metabolomics: A potential tool for more personalized medicine
By Brett Moreau | April 13th, 2018 |
The past decade has seen remarkable advances in the fields of early disease detection and personalized medicine. These advances have been made possible by “omics” technologies that have facilitated a better understanding of biological processes and associations between genetic features and disease states. Omics refers to high-throughput approaches for investigating basic cellular processes, including genomics for the investigation of DNA, transcriptomics for the investigation of gene transcripts, and proteomics for the investigation of proteins.
While most attention has been paid to genomic and transcriptomic studies, recent advances in technology have made metabolomics, the investigation of small chemical metabolites, an emerging field of omics research.
What is metabolomics?
Metabolomics measures small molecules such as sugars, amino acids, and lipids, which are the byproducts of basic biological reactions. This technique allows for differences in metabolic profiles to be linked to biological or clinical changes of interest. Unlike other omics approaches, which use differences in gene expression or protein concentration to predict functional consequences, metabolomics looks directly at the end products of gene or protein differences: metabolites that facilitate biological or clinical changes.
In addition, because metabolomics looks at a terminal endpoint in the pathway, differences in DNA, transcripts, or proteins are amplified: minor changes in the genome can result in significant differences in the metabolites released. This allows metabolomics to detect subtle differences that may be missed by other techniques. Metabolomic analysis can be performed on a variety of biological samples, such as blood, urine, or stool. As these samples are readily available and access is minimally invasive, these samples could be widely used for the detection of biomarkers that act as predictors of disease susceptibility or responsiveness to treatment.
Carrying out metabolomic studies: Untargeted versus targeted approaches
There are two major approaches for metabolomics, depending on the ultimate goal of the study:
- Untargeted metabolomic studies aim primarily to identify new metabolic compounds or changes that have not previously been associated with disease. To do this, profiles of all measurable metabolites are determined between different samples. This leads to detection of a broad coverage of metabolites, but only relative quantification of metabolite levels in a sample. While no previous knowledge of the metabolites associated with a disease state is required, it may be difficult to determine the identity of unknown compounds.
- Targeted metabolomics measures predefined metabolites of interest in samples. While this requires prior knowledge of associations between metabolite concentration and disease states, it allows more exact determination of absolute metabolite concentrations as well as easier identification of specific metabolites.
Untargeted approaches can first be used to get a basic understanding of metabolites of interest, followed by targeted approaches to quantify differences in metabolites that may contribute to disease. Metabolite detection is primarily mediated using technologies such as mass spectrometry or NMR spectroscopy, which allows for identification and quantification of heterogeneous metabolites.
Limitations of metabolomics:
While metabolomics has a number of advantages, there are also limitations that must be taken into account.
- Because metabolomics looks at the end products of biological processes, results do not identify specific genomic or protein changes that cause any difference in metabolite concentration observed.
- Another potential limitation is that, while identified metabolites can be limited or supplemented as a potential therapy, this is not always the case. It is possible that there is no causal relationship between the metabolite and disease state. Rather, differences in metabolite concentration may represent an off-target effect, making them effective as disease markers but ineffective as therapeutic interventions.
- Another drawback to metabolomic studies is the variety of unique metabolic compounds that can be detected. While genomic and proteomic studies identify molecules composed of similar structures, metabolites are a heterogeneous population of unique chemical structures. This feature can make identification of unknown compounds difficult.
Advances in metabolomics allow for the detection and identification of biological metabolites that directly impact human health. Coupling this data with clinical information allows for the association of differences in metabolic profiles and disease states, which may enhance therapy or predict individual susceptibility to disease. Metabolomics may ultimately lead to key advances in personalized medicine. In our subsequent article, we will discuss specific clinical applications of metabolomics.
Interested in exploring more breakthroughs and advances in the field of early disease diagnosis or personalized medicine? Contact us today!
Brett Moreau is a PhD candidate in Microbiology at the University of Virginia School of Medicine. His current research focuses on identification and characterization of virulence factors in bacterial pathogens. His primary interests revolve around translating research in science and technology to inform decisions and solve problems.
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- Metabolomics: A potential tool for more personalized medicine - April 13, 2018
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