The Human Metabolome Project

Metabolomics is a newborn cousin to genomics and proteomics. Specifically, metabolomics involves the rapid, high throughput characterization of the small molecule metabolites found in an organism. Since the metabolome is closely tied to the genotype of an organism, its physiology and its environment (what the organism eats or breathes), metabolomics offers a unique opportunity to look at genotype-phenotype as well as genotype-envirotype relationships. Metabolomics is increasingly being used in a variety of health applications including pharmacology, pre-clinical drug trials, toxicology, transplant monitoring, newborn screening and clinical chemistry. However, a key limitation to metabolomics is the fact that the human metabolome is not at all well characterized.

Unlike the situation in genomics, where the human genome is now fully sequenced and freely accessible, metabolomics is not nearly as developed. There are approximately 2900 endogenous or common metabolites that are detectable in the human body. Not all of these metabolites can be found in any given tissue or biofluid. This is because different tissues/biofluids serve different functions or have different metabolic roles. To date, the HMP has identified and quantified (i.e. determined the normal concentration ranges for) 309 metabolites in CSF, 1122 metabolites in serum, 458 metabolites in urine and approximately 300 metabolites in other tissues and biofluids. Clearly more concentration data would be desirable and this is one of the long term goals of the HMP and other affiliated metabolomic projects around the world.

The Human Metabolome Project is a $7.5 million Genome Canada funded project launched in January 2005. The purpose of the project is to facilitate metabolomics research through several objectives to improve disease identification, prognosis and monitoring; provide insight into drug metabolism and toxicology; provide a linkage between the human metabolome and the human genome; and to develop software tools for metabolomics.

The project mandate is to identify, quantify, catalogue and store all metabolites that can potentially be found in human tissues and biofluids at concentrations greater than one micromolar. This data will be freely accessible in an electronic format to all researchers through the Human Metabolome Database (www.hmdb.ca). In addition, all compounds will be publicly available through our Human Metabolome Library (www.metabolibrary.ca).

Already more than 800 compounds have been identified and by end of 2006, it is expected that more than 1400 metabolites will have been identified, quantified and archived into web-accessible databases (www.hmdb.ca) and stored in -80°C freezers. However, the Human Metabolome Project is only mandated to provide chemical data and chemical compounds to the scientific community. It does not have the funding or the resources to use these "raw materials" for disease identification and characterization. Indeed the intent of the Human Metabolome Project is to be an enabler of future metabolomic research, just as the Human Genome Project has been an enabler of current genomic research.

We intend to be among the first research groups in Canada to be enabled by the Human Metabolome Project. Specifically we wish to combine the analytical technologies we have already helped develop with the databases (and chemical libraries) being developed to take metabolic profiling to a new level. We believe that by combining NMR-based metabolic profiling with new data from the Human Metabolome Project, we will be able to more fully characterize and understand a wide range of important metabolic disorders. It is important to emphasize that these investigations are not a simple reassessment of well-known and well-understood metabolic disorders. Given the state-of-the-art in metabolic profiling where only a small number of metabolites are routinely identified or identifiable, we are very much at the stage where human genetics was before the advent of microarrays.