The 2005 International Conference on Metabolic Profiling entitled Using Metabolomics to Accelerate Drug Discovery and Development was held in Durham, NC, USA, November 14–15. The conference included a preconference workshop Metabolomics as an indicator for disease and personalized therapeutics. The major sessions that followed were: Biomarker and early toxicity identification and Integrating metabolomics and genomics. This meeting was an inaugural conference with a moderate attendance.
Overall, I found the meeting interesting and informative; however, I was one of the organizers of the preconference workshop. As I have recently reviewed a proteomics conference, it was clear that the focus of this meeting was quite different. Specifically, this meeting covered much of the knowledge obtained from protein discovery technology and candidate biomarkers, and how to use this to detect disease, and to understand metabolism and its relationship to drug action, toxicity and disease. Of course, the ultimate goal through understanding is to cure disease and improve health while preventing adverse events such as toxicity.
Mass spectrometry holds a key role in identification of the metabolites expressed by proteins. An expert in proteomics typically pursues questions and answers to identification or new proteins, and improved characterization of known proteins, with an emphasis on function and significance in biochemistry. The expert in metabolomics typically pursues the next set of questions after a protein has been identified, such as the results of the function of abnormal proteins and how this affects different biochemical or physiological process. A metabolomics expert typically focuses on a broad array of metabolites, such as products and precursors of proteins, as well as alterations of metabolites that have a role in regulation of protein and/or enzyme activity or function. In many ways, metabolomics is as complex as proteomics, if not more so. Integration of genomics, proteomics and metabolomics will likely be the major movement in science over the next decade, with a focus on how this improves disease identification and its treatment to a much more personalized extent than in current practice. In other words, it is how your genes interact with the environment that affects metabolism, and a person’s metabolic profile will help us monitor good health and intervene early before more severe disease occurs.
The preconference session on Metabolomics as an indicator for disease and personalized therapeutics featured an overview of the metabolomics field. Much of the focus was on the concept of the metabolic profile, metabolic signatures or metabolic fingerprints and its use in detecting and characterizing disease. Many of the approaches used in proteomics and metabolomics are similar, although the clinical analysis of metabolites is easier from a methodological standpoint, but not from an interpretive viewpoint. A key term utilized in this lecture was fluxomics. The term essentially describes the study of synthesis and utilization of metabolites. In the case of disease states, a modification in an enzyme activity (a protein) affects a metabolite, its precursors, products and other enzyme pathways for which it may regulate and, hence, its flux.
The other lectures in this preconference focused on moving towards new clinical assays, such as colon cancer and diabetes. I found two of these lectures quite intriguing. Using mass spectrometry, a series of biomarker metabolites were discovered that were well correlated with all stages of colon cancer; however, they have not been positively identified or at least revealed to the attendees. What may be important in terms of ideas in this lecture was that small molecules, generally metabolites, may be significant in a disease such as cancer. Historically, most emphasis has been in genomics and proteomics. Another presentation focused on how to understand metabolic pathway integration for the identification of disease. In a lecture by Christopher Newgard, it was clear that a metabolomics approach will not hit a motionless target with high precision, such as that of a sharpshooter, but would rather be more like a shotgun approach in which you hit a dynamic moving target and hope to hit other related targets close by.
The main session of the meeting entitled Biomarker and early toxicity identification shifted the meeting to more traditional metabolomics investigations in drug discovery and drug development. Much of the session’s focus was in the area of high-throughput, multiple metabolite profile analysis. Talks ranged from improving analytical throughput using techniques such as liquid chromatography mass spectrometry and spectroscopy, as well as more recent and powerful data systems for processing information. The session ended with lectures more ‘on topic’, such as predicting patients at risk for toxicity using stable isotopes, mass spectrometry and metabolic profiling.
Day two of the meeting was introduced with a lecture regarding the National Institutes of Health (NIH) roadmap. Essentially, it was a walk through the bureaucracy of NIH and to inform the audience as to what funding objectives were on tap at the organization and how it could impact metabolomics; in essence, where metabolomics was placed on this map. This lecture was followed by the session called Integrating metabolomics and genomics. The goal of this series of lectures was to link DNA information with their expression in metabolomics. Many lectures correlated specific genes with a phenotype or, more specifically, a metabolic profile.
The remainder of the meeting was focused on technology platforms. In an emerging field, such as metabolomics, the tools of the trade often drive the discoveries and research, and ultimately, any clinical tests that result. We heard two talks. One was focused on nuclear magnetic resonance studies to measure kinetics of systems. The other was more technology based, with a discussion of nanospray mass spectrometry and how this tool could be used to improve metabolic analysis and throughput. Finally, the last few lectures focused on the importance of examining metabolites and the interpretation of data. Lipidomics and diabetes were frequently encountered subjects. Certainly, these are two fields that require a better understanding of integrated metabolism and its affects, as well as the detection of the disease itself.
Considering this was the first conference on this topic that was held by the organizers, it was a good start. Generally, the topics touched on general themes; however, rather than providing a bridge across the river of understanding, they were more like large stones in the river that had to be skipped across to obtain an understanding of, or simply get an insight into, metabolic profiling. Clearly, metabolism is quite different from genomics and proteomics in that a metabolite is a variable parameter. Merely studying a single metabolite and correlating it to a disease, toxicity or pharmacological effect is simplistic. Metabolism is complex. It is the goal of most of the meeting attendees and lectures to find ways to better understand, define or simplify the field. Personally, I believe metabolism is where the ‘rubber meets the road’ in disease and its treatment. It is where genes and proteins express their designs, together with influences from the environment, drugs, nutrition and lifestyle. Frankly, it is this challenge and wide open areas of investigation that makes metabolomics and this meeting so interesting. In that regard, the meeting accomplished the primary goals of most meetings, which are to inform and stimulate new ideas and thoughts. In that regard, it was a clear success.