Lu Rahman speaks to key members of Metabolon on the company’s pioneering work in metabolomics including its innovative collaborations with DNAGenotek and the Institute for Systems Biology.
“Metabolon has built an unrivalled global biochemical profiling platform capable of providing metabolite data of unsurpassed quality and coverage,” says Brian Keppler, PhD, Director, Discovery and Translational Sciences at Metabolon (main image). “Also, considering our targeted assay and precision medicine capabilities as well, Metabolon has truly pioneered the field of metabolomics.”
The Discovery and Translational Sciences team at Metabolon provides actionable biological insights into the company’s pharma, biotech and applied markets clients.
The root cause of the common challenges through drug discovery and development is not having a clear picture of what is going on, or not possessing a direct biomarker to track such processes. To overcome this obstacle, tools and assays that delve deeply into this ‘murkiness’ with high fidelity are needed. Metabolomics is well-suited to augment decision-making across the drug development process as it is comprehensive (unlike other approaches, it will produce few blind spots), meaningful and readily interpreted, and it dynamically assesses a living system and links it to physiological changes induced by disease and drug response (unlike other tools and data streams, which are less proximal to where the ‘action’ occurs).
Metabolomics has emerged as a powerful tool for the progression of precision medicine and Metabolon is committed to leading the advancement of clinical metabolomics to transform precision medicine and advance diagnosis and treatment of patients suffering from rare and undiagnosed diseases.
Bryan Wittmann, PhD, Director of Discovery and Translational Sciences for Clinical Metabolomics and Population Health at Metabolon, says: “Precision medicine encompasses an individual’s genes, environment and lifestyle in order to identify, treat and prevent disease and all these factors impact an individual’s biochemical profile. Metabolomics functions at the intersection between these factors impacting an individual’s health status and the phenotypic manifestation of the disease and can identify disease signatures prior to a change in phenotype of a patient and in many cases the severity of the disease.”
These insights help to increase the success of a treatment administered to a patient. “One of the major hurdles in both rare disease detection and overall individual wellness is the ability to rapidly screen for underlying disease and monitor treatment. Due to the broad coverage of hundreds of biochemicals covering multiple biochemical pathways, metabolomics can overcome these hurdles in a single blood sample through its ability to quickly screen for disease biomarkers that can also function as a read-out for treatment efficacy,” adds Wittmann.
Metabolon recently collaborated with DNAGenotek on ambient temperature microbiome sampling. “It was the right time for both companies,” says Keppler. “DNAGenotek was aware of the growing metabolomics market and the need for ambient temperature collection of faeces, and Metabolon had received consistent customer requests to have an ambient temperature collection method. Our customers had tried to use the OMNIgene·GUTdevice that was made by DNAGenotek, but it wasn’t designed to work for metabolomics. So, conversations started between the product R&D team at DNAGenotek and the analytical R&D team at Metabolon to examine feasibility for a collaboration that recently brought OMNImet·GUT to the research market, the first device for in-home collection and ambient-temperature storage and shipping of faecal samples for metabolomics.”
The collaboration brings expertise to the market and has an impact on metabolomic research.The availability of OMNImet·GUTwill allow patients/donors to collect samples at home or at other readily available sites lacking previously required storage capabilities, making it easier to recruit subjects and complete research. This will provide a trusted, proven, and familiar way to collect faecal samples at ambient temperature to perform validated metabolomics research. “The possibilities and scenarios for researchers to collect samples has expanded beyond what was imaginable before this collaboration. New research that simply wasn’t possible will follow suit,” Keppler continued.
It is evident that metabolomics has a key role to play in drug discovery offering huge potential for the sector and the way it understands disease and advances new treatments.
Much of the innovation supporting recent advancements in life science research have been genomic based. While that provides great directional insight, a functional understanding of the underlying mechanisms has been missing. Because of the unique capability of metabolomics to reveal function, it has been particularly valuable in deciphering the microbiome. As the complexity of research continues to rise, metabolomics is already playing an increasing role by revealing function, identifying new biomarkers and providing other actionable insights. “When combined with genomics or other methods, metabolomics provides the link that was needed to begin to deliver on the promise of a multi-omics approach to improve life science research,” reveals Keppler.
Metabolon has also partnered with the Institute for Systems Biology – founded in 2000 as the first institute dedicated to systems biology – to investigate disease severity among COVID-19 patients. One of the defining features of COVID-19 disease is the substantial variability in disease progression, severity and outcomes. This important study will help to quantify and characterize this heterogeneity through the application of machine learning algorithms that are capable of integrating molecular information about the patient for the purpose of identifying subgroups within the patient population based on biomarker data. ISB is a world leader in understanding complex data sets and applying this knowledge for improving health. They have unique access to a deeply studied healthy control cohort that makes them an ideal partner for this type of study.
With this in mind Wittmann explains more about the collaboration and its aims: “Over a one-year period, 200 patient samples are being collected from Seattle patients with different COVID-19 disease severity. These samples will be collected over multiple time points. The project is expected to be expanded to include other health research partner organizations on the West Coast of the US.
The data will be beneficial in addressing the current COVID-19 crisis as well as helping map a response for future outbreaks. “There is an urgent need to understand who is at highest risk of developing severe disease,” says Wittman. “The insights from this study will be useful to inform current clinical practice as well as selection of the right treatment.”
A primary goal of this study is the identification, via a comprehensive metabolomic analysis of blood biomarkers, of the molecular pathways that are perturbed by SARS-CoV-2 virus infection, using measurements that index immune system and organ function. Metabolomics can supplement traditional clinical measurements to identify unique biomarkers that can classify those patients at highest risk for serious adverse effects of COVID-19.
Rohan Hastie, President and CEO, Metabolon, underlines the importance of Metabolon’s study:“The entire scientific community is working overtime to find answers that will deliver effective therapeutics and prevention strategies to overcome the coronavirus pandemic. This is a time when partnerships in the scientific community are essential to uncover solutions, quickly. We are pleased to collaborate with ISB to deliver our metabolomics expertise to this important work.”
Volume 21, Issue 4 – Fall 2020