Glycomics
Glycomics is the comprehensive study of glycomes[1] (the entire complement of sugars, whether free or present in more complex molecules of an organism), including genetic, physiologic, pathologic, and other aspects.[2][3] Glycomics "is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology.[4] The term glycomics is derived from the chemical prefix for sweetness or a sugar, "glyco-", and was formed to follow the omics naming convention established by genomics (which deals with genes) and proteomics (which deals with proteins).
Challenges
- The complexity of sugars: regarding their structures, they are not linear instead they are highly branched. Moreover, glycans can be modified (modified sugars), this increases its complexity.
- Complex biosynthetic pathways for glycans.
- Usually glycans are found either bound to protein (glycoprotein) or conjugated with lipids (glycolipids).
- Unlike genomes, glycans are highly dynamic.
This area of research has to deal with an inherent level of complexity not seen in other areas of applied biology.
Add to this the complexity of the numerous proteins involved, not only as carriers of carbohydrate, the glycoproteins, but proteins specifically involved in binding and reacting with carbohydrate:
- Carbohydrate-specific enzymes for synthesis, modulation, and degradation
- Lectins, carbohydrate-binding proteins of all sorts
- Receptors, circulating or membrane-bound carbohydrate-binding receptors
Importance
To answer this question one should know the different and important functions of glycans. The following are some of those functions:
- recognition.
- They are involved in cellular signaling pathwaysand modulate cell function.
- They are important in innate immunity.
- They determine cancer development.
- They orchestrate the cellular fate, inhibit proliferation, regulate circulation and invasion.
- They affect the stability and folding of proteins.
- They affect the pathway and fate of glycoproteins.
- There are many glycan-specific diseases, often hereditary diseases.
There are important medical applications of aspects of glycomics:
- Lectins fractionate cells to avoid graft-versus-host disease in hematopoietic stem cell transplantation.
- Activation and expansion of cytolytic CD8 T cells in cancer treatment.
Glycomics is particularly important in microbiology because glycans play diverse roles in bacterial physiology.[7] Research in bacterial glycomics could lead to the development of:
- novel drugs
- bioactive glycans
- glycoconjugate vaccines
Tools used
The following are examples of the commonly used techniques in glycan analysis[4][5]
High-resolution mass spectrometry (MS) and high-performance liquid chromatography (HPLC)
The most commonly applied methods are MS and HPLC, in which the glycan part is cleaved either enzymatically or chemically from the target and subjected to analysis.[8] In case of glycolipids, they can be analyzed directly without separation of the lipid component.
N-
O-
Fractionated glycans from
In recent years, high performance liquid chromatography online coupled to mass spectrometry became very popular. By choosing porous graphitic carbon as a stationary phase for liquid chromatography, even non derivatized glycans can be analyzed. Electrospray ionisation (ESI) is frequently used for this application.[13][14][15]
Multiple Reaction Monitoring (MRM)
Although MRM has been used extensively in metabolomics and proteomics, its high sensitivity and linear response over a wide dynamic range make it especially suited for glycan biomarker research and discovery. MRM is performed on a triple quadrupole (QqQ) instrument, which is set to detect a predetermined precursor ion in the first quadrupole, a fragmented in the collision quadrupole, and a predetermined fragment ion in the third quadrupole. It is a non-scanning technique, wherein each transition is detected individually and the detection of multiple transitions occurs concurrently in duty cycles. This technique is being used to characterize the immune glycome.[16][17][18]
Table 1: Advantages and disadvantages of mass spectrometry in glycan analysis
Advantages | Disadvantages |
---|---|
|
|
Arrays
Lectin and antibody arrays provide high-throughput screening of many samples containing glycans. This method uses either naturally occurring
Glycan arrays, like that offered by the Consortium for Functional Glycomics and Z Biotech LLC, contain carbohydrate compounds that can be screened with lectins or antibodies to define carbohydrate specificity and identify ligands.
Metabolic and covalent labeling of glycans
Metabolic labeling of glycans can be used as a way to detect glycan structures. A well known strategy involves the use of
Tools for glycoproteins
Software and databases
There are several on-line software and databases available for glycomic research. This includes:
See also
- Cytomics
- Glycobiology
- GlycomeDB
- UniCarb-DB
- Carbohydrate Structure Database (CSDB)
- Glycoconjugate
- Glyquest
- Interactomics
- Lipidomics
- List of omics topics in biology
- Metabolomics
- Omics
- Proteomics
- systems biology
- Minimum Information Required About a Glycomics Experiment
References
- ISBN 9781621821328.)
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: CS1 maint: location missing publisher (link - PMID 18516240.
- PMID 18509903.
- ^ ISBN 978-087969770-9.
- ^ hdl:1874/364403.
- ^ ucsd news article Do 68 Molecules Hold the Key to Understanding Disease? published September 3, 2008
- ISBN 978-1-904455-95-0.
- PMID 17223647.
- PMID 743278.
- PMID 18940176.
- .
- PMID 11114021.
- PMID 12498206.
- PMID 17539604.
- S2CID 43431212.
- S2CID 195759019.
- PMID 25578468.
- PMID 23457413.
External links
- glycosciences.de This site provides databases and bioinformatics tools for glycobiology and glycomics.
- GlycomeDB, A carbohydrate structure metadatabase
- GlycoBase A web HPLC/UPLC resource that contains elution positions expressed as glucose unit values.
- ProGlycAn A short introduction to glycan analysis and a nomenclature for N-Glycans
- Emanual Maverakis; et al. "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity" (PDF).
- CD BioGlyco This site provides database and tools in the field of glycomics, from glycan release, separation, and purification, glycan derivatization to glycan characterization and quantification.