Human Metabolome Project

The Human Metabolome Project is a $7.5 million project launched in January 2005 and funded by Genome Canada. 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.

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. It is estimated that only a quarter to half of endogenous human metabolites in blood or urine have been positively identified. Of those that have been identified, very few have any information on their normal concentration ranges. Further, there is no publicly available, electronic database for human metabolites (i.e. no "Metabo-Bank") and there are no "metabolite libraries" which allow researchers to obtain quantities of rare metabolites from which to standardize their instruments.

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 (http://www.hmdb.ca). In addition, all compounds will be publicly available through the Human Metabolome Library (http://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 (http://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.

The project's organizers say that they intend to be among the first research groups in Canada to be enabled by the Human Metabolome Project. Specifically they 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. They believe that by combining NMR-based metabolic profiling with new data from the Human Metabolome Project, they 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, scientists are very much at the stage where human genetics was before the advent of microarrays.

The project is maintained by David Wishart of the University of Alberta.