2. • 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.
3.
4. An overview of the four major
"omics" fields, from genomics to
metabolomics
5.
6. • 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.
7. • 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
8. • 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
• 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.
9. A diagramshowing the main different types of metabolic reactionsthat take placein a
cell. Theseareshownas they arerepresented in the database Reactome.
Metabolomics - a 'snapshot' in time
11. • 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.
12. • 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
13. 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.
Applications
14. Biomarker discovery
• Biomarkerdiscovery is anotherareawheremetabolomics informs
decision making. Biomarkersare "objective indications of medical
state observed from outside the patient - which can be measured
accuratelyand reproducibly" . In metabolomics, biomarkers
are small molecules (metabolites) that can be used to distinguish
two groupsof samples, typicallyadiseaseand controlgroup.
• For example, a metabolite reliablypresent in disease samples, but
not in healthy individualswould beclassed as a biomarker. Samples
of urine, saliva, bile, or seminal fluid contain highly informative
metabolites, and can be readilyanalyzed through metabolomics
fingerprinting or profiling, for the purpose of biomarkerdiscovery
.
15. Personalized medicine
• Personalized medicine, the ultimate customization of healthcare, requires
metabolomicsforquick medical diagnosis to identify disease.
• In healthcare, we currently use classical biochemical tests to measure
individual metaboliteconcentrations to identify diseasestates (e.g. the
blood-glucoselevel in thecaseof diabetes).
• Metabolomicsoffers the potential for the rapid identification of hundreds
of metabolites, enabling us to identify these diseasestates much earlier.
17. Target analysis
• Targetanalysis has been applied for manydecadesand
includes the determination and quantification of a small set
of known metabolites (targets) using one particular
analytical techniqueof best performancefor thecompounds
of interest.
18. Metabolite profiling,
• Metabolite profiling, on the other hand, aims at the
analysis of a largerset 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 plasmasamples .
19. Metabolomics
• Metabolomics employs complementaryanalytical
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.
20. metabolic finger-printing
• The fourth conceptual approach is metabolic finger-printing (or foot
printing forexternal and/orsecreted metabolites). Herea metabolic
“signature”or mass profileof 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 aredetected, the metabolitesare identified and the biological
relevanceof that compound can beelucidated, greatly reducing the
analysistime.
21. metabolomics and some more uses
• phenotyping of geneticallymodified plants
• substantial equivalence testing
• determination of gene function
• monitoring responsesto bioticand abioticstress.
• Metabolomicscan thereforebe seen as bridging the gap betweengenotypeand
phenotype .
• providea morecomprehensiveview of howcells function, as well as identifying
novel orstriking changes in specific metabolites.
• Analysisand data mining of metabolomicsdata setsand their metadatacan also
lead to new hypothesesand new targets for biotechnology.