Metabolomics and the Human Metabolome Project

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Metabolomics and the Human Metabolome
Project David Wishart Lori Querengesser,
University of Alberta, Edmonton, Canada
Abstract Metabolomics involves the rapid, high
throughput characterization of the small molecule
metabolites found in an organism. 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. To address these issues we have
initiated the Human Metabolome Project, with the
aim of completing the human metabolome by 2007.
This will involve identifying, spectroscopically
characterizing (via NMR and MS), 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. This project will combine high
throughput NMR methods along with FT-MS and other
analytical techniques to identify and quantify
metabolite and their concentration ranges from a
large number of human samples. The data and the
compounds isolated, synthesized or purchased from
this project will be used to create a freely
available electronic database called the human
metabolite database (HMDB) and a commercial
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.
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
Over the next 2 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
1399 metabolites and placed them into a first
draft of an on-line human metabolite database
(HMDB). It is available at http//www.hmdb.ca To
date 381 chemical compounds have been purchased
or acquired and another 420 have been identified
as the next to be acquired, synthesized or
isolated.
The Pyramid of Life, a diagram illustating the
relationship between metabolomics, genomics and
proteomics.
The Human Metabolome Project brings together 8
Principal Investigators from a broad variety of
backgrounds including clinical chemistry,
biochemistry, analytical chemistry, organic
chemistry computing science. Another 20
individuals are expected to be hired to work on
various aspects of the project.
Screenshot montage of the Human Metabolome
Database web pages. These shots show examples of
the browser/sorter (top), and the metabocard
for each metabolite (50 fields of data left
and right). All metabolites will be linked to
known biochemical pathway diagrams and enzyme or
gene data.
We are always looking for new collaborators. We
presently have collaborators in the areas of
cachexia, prostate cancer, obesity, and
pneumonia. We have equipment (NMR, HPLC, FT-ICR,
QTOFs, etc) ready and waiting for samples to be
analyzed and have 4 full-time programmers to
develop software you may need.