Abstract: Unlike the situation in genomics, where the human genome is now fully sequenced and freely

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Metabolomics and the Human Metabolome
Project David Wishart Lori Querengesser,
University of Alberta, Edmonton, Canada
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.
Introduction
Project Workflow
The HMDB
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.
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 http//redpoll.pharmac
y.ualberta.ca 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.
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.
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
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!
Metabolomics Tools
Metabolomics Proteomics Genomics
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
1400?? Chemicals
3000 Enzymes
30,000 Genes
Brian Sykes Biochemistry U of Alberta NMR spect.
Russ Greiner Comp. Sci. U of Alberta Bioinformatic
s
David Wishart Comp. Sci. U of Alberta Proj. Leader
Hans Vogel Biochemistry U of Calgary NMR spect.
Figure 1. The Pyramid of Life, a diagram
illustating the relationship between
metabolomics, genomics and proteomics.
A Modest Proposal
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.
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
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/Separati
on.