The Road Less Traveled: The Faster Path to Biological Insights
Researchers continue to mine the genome for clues that assist in understanding susceptibility to disease, selection of targets for combating disease, and the biomarkers indicating response. Surprisingly, though, a fast and valuable source of data that can either lead or strengthen this pursuit is not always part of the equation.
What’s Missing in Your Research?
While we should retain our commitment to understanding biology through standard cell and molecular biology tools, it is important to remind ourselves that metabolites have been, and continue to be, a staple for clinical and in vivo decision making.
- Well-known metabolites, such as glucose, cholesterol, creatinine, bilirubin and thyroid hormone, are used as routine barometers for assessing diabetes, heart disease, renal, hepatic and thyroid function.
- In screening newborns for inborn errors of metabolism (IEMs), the levels of certain blood metabolites are used as surrogates for signifying a clinical condition arising from a genetic mutation.
- Importantly, more subtle phenotypes, such as susceptibility to a disease, response to a drug, or prognosis, may also have a biochemical “fingerprint.”
There is a strong, well-established association between the metabolite and the phenotype. In fact, this understanding formed the basis of almost a century of metabolic investigation from famous researchers including Krebs, Warburg, Cori and Pasteur.
Despite this, the last several decades have intensely focused on the molecular genetic basis of biology. Metabolism research didn’t fade because it lacked value in understanding biology; it was simply the genuine and vigorous interest in gene function that relegated it to a less favored life science discipline.
Although undeniably important as our foundational blueprint, DNA reflects the risk or potential for disease. In many instances, though, a complex network of genes, transcripts, proteins and regulation conspires with the environment and microbiome to result in a physiological or phenotypic change.
Key to the value of metabolites is that they may reflect all of these factors, and metabolites themselves may play an integral role in the activity of genes and proteins through epigenetic alterations and post-translational modifications.
From a biomarker discovery perspective, metabolites are particularly attractive since they can be identified from any biological sample type, including cells, media, tissues, body fluids, and even exhaled breath condensate.
In addition, since metabolism is central to all living things, many pathways are highly conserved, making findings particularly translatable across species. Therefore, if a biomarker is identified in a pre-clinical model, it has a strong potential to have relevance in human disease.
Advances in Metabolomics Technology Speed the Path
So, why aren’t metabolites routinely surveyed to address biomarker and R&D objectives? Aside from the genomic focus mentioned above, another issue at the heart of this question is the fact that building the technology is extremely challenging. Until recently, technologies that could fully exploit the information embedded in the metabolome did not exist.
Given the chemical diversity of metabolites (e.g., carbohydrates, organic acids, lipids, etc.), immense technical challenges existed in tapping into this data stream, but a key advance came from the development of software tools that could provide rapid metabolite identification and QC of the data. Today, metabolomics, the technology for widespread metabolic analysis, offers an extremely effective, accurate means for examining metabolism.
Metabolomics can be done on an industrial scale resulting in the discovery of novel biomarkers and actionable biological insight. As appreciated by over a century of biochemistry and contemporary clinical testing, surveying metabolism offers an integrated vantage-point for understanding complex biological states, such as disease or drug response. The signatures that accompany these states can serve as clinically useful biomarkers.
We Have a Biomarker! What’s Next?
Metabolomics frequently produces unexpected biomarkers and disease insight, even in extensively studied disease states. Perhaps the best example of this is in cancer, where it is now appreciated that all major oncogenic drivers induce a change in the metabolic phenotype.
Metabolomic studies in recent years, as evidenced by the proliferation of peer-reviewed publications (including top journal publications), have led to breakthroughs in disease understanding and treatments. Like genomics, metabolomics offers value in any biological research area. In fact, metabolomics has resulted in successful outcomes in numerous fields, including oncology, metabolic disease, cardiovascular disease, respiratory and rare diseases.
No matter the disease area, metabolites are an important probe of phenotypic or physiological inquiry that goes beyond genomics. Metabolomics has matured to a point where meaningful advancement of biological insights and identification of sensitive and specific biomarkers can occur in a range of different diseases.
Metabolomics applications continue to grow and provide unprecedented knowledge for clinicians and life sciences researchers across many industries and academic and government organizations. This expanding technology for biomarker discovery is now routinely used in disease research, pharmaceutical development, nutrition and agriculture. Metabolomics is also rapidly moving into clinical applications to promote wellness and diagnose and treat diseases.
If you’d like to learn how to add metabolomics to your research, please contact us.