5. • Metabolomics is the systematic study of the metabolome, the unique
biochemical fingerprint of all cellular processes
• Metabolomics is the large-scale study of small molecules, commonly known as
metabolites, within cells, biofluids, tissues or organisms. Collectively, these small
molecules and their interactions within a biological system are known as the
metabolome.
• Metabolomics is the systematic study of the small molecular metabolites in a
cell, tissue, biofluid, or cell culture media that are the tangible result of cellular
processes or responses to an environmental stress.
• The metabolome is the total complement of metabolites present in a biological
sample under given genetic, nutritional or environmental conditions.
• Metabolomics technologies yield many insights into basic biological research in
areas such as systems biology and metabolic modelling, pharmaceutical research,
nutrition and toxicology.
6.
7. An overview of the four major
"omics" fields, from genomics to
metabolomics
8. • Just as genomics is the study of DNA and genetic information within a
cell, and transcriptomics is the study of RNA and differences in mRNA
expression; metabolomics is the study of substrates and products
of metabolism, which are influenced by both genetic and environmental
factors .
• Metabolomics is a powerful approach because metabolites and their
concentrations, unlike other "omics" measures, directly reflect the
underlying biochemical activity and state of cells / tissues. Thus
metabolomics best represents the molecular phenotype.
11. • A small molecule (or metabolite) is a low molecular weight organic compound,
typically involved in a biological process as a substrate or
product. Metabolomics usually studies small molecules within a mass range of 50 –
1500 daltons (Da).
• Some examples of small molecules include: sugars, lipids, amino acids, fatty acids,
phenolic compounds, alkaloids and many more
13. • The metabolome is the complete set of metabolites within a cell, tissue or
biological sample at any given time point. The metabolome is inherently very
dynamic: small molecules are continuously absorbed, synthesised, degraded
and interact with other molecules, both within and between biological systems,
and with the environment (fig:3)
• Many reactions take place continuously within cells, so concentrations of
metabolites are considered to be very dynamic, and may change rapidly from
one time point to the next. Current analytical techniques used to investigate
metabolomics can only take a snapshot in time under a set of defined
conditions.
14. A diagram showing the main different types of metabolic reactions that take place in a
cell. These are shown as they are represented in the database Reactome.
Metabolomics - a 'snapshot' in time
16. • Metabolic pathways are essentially a series of chemical reactions, catalyzed by
enzymes, whereby the product of one reaction becomes the substrate for the
next reaction. These reactions can be divided into anabolic and catabolic.
• The non-invasive nature of metabolomics and its close link to the phenotype
make it an ideal tool for the pharmaceutical, preventive healthcare, and
agricultural industries, among others. Biomarker discovery and drug safety
screens are two examples where metabolomics has already enabled informed
decision making. In the future, with the availability of personalized
metabolomics, we will potentially be able to track the trends of our own
metabolome for personalized drugs and improved treatment strategies.
Personalized treatment is likely to be more effective than our current medical
population-based approaches.
18. • We benefit from metabolomics on various levels: from product and stress
testing in food industries, e.g. control of pesticides and identification of
potentially harmful bacterial strains, to research in agriculture (crop
protection and engineering), medical diagnostics in healthcare, and
future applications in personalized medicine resulting in personliased
treatment strategies
20. Agricultural
• The development of new pesticides is critical to meet the growing demands
on farming. Metabolomics enables us to improve genetically modified plants,
and helps us to estimate associated risks by allowing us to get a glimpse of
their complex biochemistry via informative snapshots acquired at different
time points during plant development.
• Plant metabolomics is particularly interesting because of the range and
functions of primary and secondary metabolites in plants. About 300 distinct
metabolites could be routinely identified per sample a decade ago, and the
number is gradually increasing over time.
21. Biomarker discovery
• Biomarker discovery is another area where metabolomics informs
decision making. Biomarkers are "objective indications of medical
state observed from outside the patient - which can be measured
accurately and reproducibly" . In metabolomics, biomarkers
are small molecules (metabolites) that can be used to distinguish
two groups of samples, typically a disease and control group.
• For example, a metabolite reliably present in disease samples, but
not in healthy individuals would be classed as a biomarker. Samples
of urine, saliva, bile, or seminal fluid contain highly informative
metabolites, and can be readily analyzed through metabolomics
fingerprinting or profiling, for the purpose of biomarker discovery.
22. Personalized medicine
• Personalized medicine, the ultimate customization of healthcare, requires
metabolomics for quick medical diagnosis to identify disease.
• In healthcare, we currently use classical biochemical tests to measure
individual metabolite concentrations to identify disease states (e.g. the
blood-glucose level in the case of diabetes).
• Metabolomics offers the potential for the rapid identification of hundreds
of metabolites, enabling us to identify these disease states much earlier.
23. conceptual approaches
There are four conceptual approaches in metabolomics:
• Target analysis
• Metabolite profiling
• Metabolomics
• Metabolic fingerprinting
24. Target analysis
• Target analysis has been applied for many decades and
includes the determination and quantification of a small set
of known metabolites (targets) using one particular
analytical technique of best performance for the compounds
of interest.
25. Metabolite profiling,
• Metabolite profiling, on the other hand, aims at the
analysis of a larger set of compounds, both identified and
unknown with respect to their chemical nature. This
approach has been applied for many different biological
systems using GC-MS, including plants , microbes ,urine
,and plasma samples .
26. Metabolomics
• Metabolomics employs complementary analytical
methodologies, for example, LC-MS/MS, GC-MS, and/or
NMR, in order to determine and quantify as many
metabolites as possible, either identified or unknown
compounds.
27. metabolic finger-printing
• The fourth conceptual approach is metabolic finger-printing (or foot
printing for external and/or secreted metabolites). Here a metabolic
“signature” or mass profile of the sample of interest is generated and then
compared in a large sample population to screen for differences between
the samples. When signals that can significantly discriminate between
samples are detected, the metabolites are identified and the biological
relevance of that compound can be elucidated, greatly reducing the
analysis time.
28. metabolomics and some more uses
• phenotyping of genetically modified plants
• substantial equivalence testing
• determination of gene function
• monitoring responses to biotic and abiotic stress.
• Metabolomics can therefore be seen as bridging the gap between genotype and
phenotype .
• provide a more comprehensive view of how cells function, as well as identifying
novel or striking changes in specific metabolites.
• Analysis and data mining of metabolomics data sets and their metadata can also
lead to new hypotheses and new targets for biotechnology.