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Metabolomics: A Key to Realizing the Power of ‘Big Data’

inCapabilities, Omics

Big data initiatives to understand individual health, disease, and therapeutic responses are underway using a wide range of ‘omics and clinical assessment tools across a variety of large cohorts in population health studies.

When it comes to understanding the drivers of health and disease, each person’s genetic profile is important in determining risks. However, factors independent of our genes – including the composition and activity of the microbiome, which is shaped predominantly by environmental factors – also have a profound impact on health and lifespan, influencing virtually every human disease, according to Metabolon president and CEO Dr. Rohan Hastie. Hastie spoke at the 2019 Big Data in Healthcare conference, hosted by the Weizmann Institute of Science in collaboration with Nature Medicine.

While genes illustrate risk of disease, metabolites illuminate the cause and manifestation of disease. This is where metabolomics – the study of chemical processes involving small molecules known as metabolites – comes into its own. The metabolome represents the integration of genetic information with the sum of all exogenous factors – including diet, xenobiotics, lifestyle and the exposome, a measure of all the exposures of an individual in a lifetime – and how these impact health.

As the keystone of systems biology, metabolomics provides a definitive molecular measurement of the phenotype, or characteristics that result from environmental and biologic interactions with the genotype. Changes in metabolites caused by disease processes can be used to identify clinically relevant areas of the genome and to functionally map genetic variants. This drives an increased understanding of disease outcomes, patient biology and all the ‘omics – and concrete progress towards precision medicine.

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For example, we’ve known for more than 80 years that rodents given a restricted-calorie diet live longer than those allowed to feed at will, showing the important role of metabolism in the early onset of disease.[1] Metabolomics allows us to gain a deeper understanding of this process by integrating big data from genetics and transcriptomics, and mapping these to health outcomes.

During its nearly 20-year history, Metabolon has built a unique repository of metabolomic biological insight, creating the world’s largest – and continuously growing – library of biologically relevant metabolites. This expansive knowledgebase has enabled Metabolon to leverage data to help address some of the most pressing needs in life sciences research, as outlined in the examples below.

Metabolomics Success Story 1:

New therapeutic targets identified in Sickle Cell Disease

Challenge: Sickle cell disease (SCD), an untreatable group of inherited red blood cell disorders, is caused by a single point mutation. Production of abnormal hemoglobin can cause red blood cells to become sickle shaped, blocking blood flow, and causing pain and damaging many other issues.[2] In sub-Saharan Africa, some 300,000 babies are born with SCD each year; in the United States, about 100,000 people live with the disease.[3] [4] Mechanism-specific treatment options have remained elusive.

Insight from metabolomics: Metabolon has used metabolomics to advance understanding of the disease biology of SCD in preclinical models (mice overexpressing the mutant gene) and confirmed these results in humans.

Future promise: Several pathways and novel targets have been identified, including adenosine metabolism and lysophospholipids. These may be promising targets for new therapies.

Metabolomics Success Story 2:

Marrying metabolomics with genomics:
The role of hexadecanedioate in high blood pressure

Challenge: High blood pressure is a major contributor to the global burden of disease, affecting around 29% of U.S. adults.[5] By 2020, over 1.5 billion people are forecast to have high blood pressure, and two-thirds will not achieve target control with current therapeutics. Discovering novel causal pathways of blood pressure regulation has been challenging.

Insight from metabolomics: Metabolon co-authored a paper revealing a novel functional association between hexadecanedioate, a dicarboxylic fatty acid, and increased blood pressure.

Future promise:  The rising incidence of high blood pressure highlights the need for new treatments, potentially based on hexadecanedioate as a novel and important target.

An experienced partner can advance your projects using metabolomics. Metabolon is uniquely able to help clients by delivering four core capabilities essential for a truly comprehensive metabolomics offering:

  • Coverage: The ability to see and compare thousands of molecules to reveal new insights and opportunities across diverse markets
  • Competency: The ability to generate high-quality data, accompanied by the ability to derive biological insights to make actionable recommendations
  • Comparability: The ability to compare the data of different researchers, in different geographies, over time, and among different patients, races and matrices
  • Capacity: The ability to process hundreds of thousands of samples quickly and cost-efficiently to service rapidly growing demand

These elements are critical to effectively capture metabolomics big data and insights from large-scale population cohorts, and to combine these with genetic data, to provide actionable insights. Partner with Metabolon to benefit from our robust platform and visualization tools, expand knowledge of your molecule, and develop assay panels to zero in on the results you need.

If you’re ready to harness true value of metabolomics, contact us at [email protected]

References:

[1] McDonald RB, Ramsey JJ. Honoring Clive McCay and 75 years of calorie restriction research. J Nutr. 2010;140(7):1205–1210. doi:10.3945/jn.110.122804: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884327/

[2] https://www.hematology.org/Newsroom/Press-Releases/2019/9614.aspx

[3] https://www.hhs.gov/blog/2019/06/19/coming-together-to-confront-sickle-cell-disease.html

[4] https://www.cdc.gov/ncbddd/sicklecell/data.html

[5] https://www.cdc.gov/nchs/products/databriefs/db289.htm

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