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Abstract: Unlike the situation in genomics, where the human genome is now fully sequenced and freely accessible, metabolomics is not nearly as developed.

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Presentation on theme: "Abstract: Unlike the situation in genomics, where the human genome is now fully sequenced and freely accessible, metabolomics is not nearly as developed."— Presentation transcript:

1 Abstract: 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 ¼ to ½ 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 researcher to obtain quantities of rare metabolites from which to standardize their instruments. As part of our newly funded Genome Canada project we are working towards completing the human metabolome. This will involve identifying, characterizing, and quantifying an estimated 1400 endogenous metabolites that can be found in urine, blood, CSF and white blood cells at concentrations greater than 1 micromolar. The data and the compounds isolated, synthesized or purchased from this work will be used to create a freely available electronic database – called the human metabolite database (HMDB) and an open access chemical warehouse – called the human metabolite library (HML) with mg-gram quantities of these metabolites. 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 an organisms genotype, 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-environment 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. Introduction A Modest Proposal It is estimated that only ¼ to ½ 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. As part of our newly funded Genome Canada project we are working towards completing the human metabolome. This will involve identifying and quantifying an estimated 1400 endogenous metabolites that can be found in urine, blood, CSF and white blood cells at concentrations greater than 1 micromolar. The data and the compounds isolated, synthesized or purchased from this work will be used to create a freely available electronic database – called the human metabolite database (HMDB) and an open access warehouse of chemicals – called the human metabolite library (HML). Project Participants Over the next 2.5 years we expect to compile detailed data (spectra, phys-chem parameters, and concentration data) on most kinds of human metabolites. Already we have compiled data on 200 metabolites and placed them into a first draft of an on-line human metabolite database (HMD). It is available at To date 300 chemical compounds have been purchased or acquired and another 400 have been identified as the next to be acquired, synthesized or isolated. Approximately 100 new compounds are added to the database every month. Metabolomics and the Human Metabolome Project David Wishart & Lori Querengesser, University of Alberta, Edmonton, Canada A project of this type requires considerable coordination between mutliple labs. Using models originally developed for the Human Genome Project we have devised the following workflow. Figure 2. Screen shot montage of the Human Metabolome Database web pages. These shots show examples of the browser/sorter (top), the metabocard for each metabolite (50+ fields of data – left), the structure viewing applet (right) and the structure query tool to allow individuals to search by structure similarity (bottom). All metabolites will be linked to known biochemical pathway diagrams and enzyme or gene data. The Human Metabolome Project brings together 8 PIs from a broad variety of backgrounds including clinical chemistry, biochemistry, analytical chemistry, organic chemistry & computing science. It is expected that another 20 individuals will be hired to work on various aspects of the project. We are hiring now! The HMDB 30,000 Genes 3000 Enzymes 1400?? Chemicals Metabolomics Proteomics Genomics Figure 1. The Pyramid of Life, a diagram illustating the relationship between metabolomics, genomics and proteomics. Brian Sykes Biochemistry U of Alberta NMR spect. Russ Greiner Comp. Sci. U of Alberta Bioinformatics David Wishart Comp. Sci. U of Alberta Proj. Leader Hans Vogel Biochemistry U of Calgary NMR spect. Fiona Bamforth Clin. Chemistry U of Alberta Sample Acq. Derrick Clive Chemistry U of Alberta Synthesis Liang Li Chemistry. U of Alberta MS/Separation Mike Ellison Biochemistry U of Alberta MS/Separation. Project Workflow Patient Pool Prelim Bio. Sample Acquisition, prep and GC/MS characterization F. Bamforth Ethics Board Approvals Compound ID Lit Search Data Mining Greiner/Wishart Compound Purchase and Archiving Wishart HMDB web page LIMS, Sys Admin Wishart/Greiner Project Admin & Coordination Wishart/PM/AA Compound Characterization NMR Wishart/Sykes Compound Characterization FT-ICR MS Ellison/Li Compound Quantitation NMR Vogel Further Cmpd Separation And Isolation Wishart/Li/Ellison Compound ID & Characterization NMR/MS Wishart/Sykes/Li Vogel/Ellison Compound Synthesis Clive 1.5 FTE 2 FTE 1 FTE 5 FTE 1 FTE 3 FTE 1 FTE 2 FTE1 FTE High throughput metabolic profiling or metabolomics involves using either NMR, FT-MS or HPLC methods. We will be using all 3 kinds of instruments to characterize 3 different kinds of compounds: 1) purchased 2) synthesized & 3) isolated from biofluids Metabolomics Tools


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