# Glycomics > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Glycomics > Markdown URL: https://mediated.wiki/source/Glycomics.md > Source: https://en.wikipedia.org/wiki/Glycomics > Source revision: 1346335824 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{Short description|Study of glycomes}} '''Glycomics''' is the comprehensive study of [glycome](/source/glycome)s{{cite book |last1=Rudd |first1=Pauline |last2=Karlsson |first2=Niclas G. |last3=Khoo |first3=Kay-Hooi |last4=Packer |first4=Nicolle H. |editor1-last=Varki |editor1-first=Ajit |title=Essentials of glycobiology |date=2017 |location=Cold Spring Harbor, New York |isbn=978-1-62182-132-8 |edition=Third |chapter=Chapter 51: Glycomics and Glycoproteomics}} (the entire complement of [sugar](/source/sugar)s, whether free or present in more complex [molecule](/source/molecule)s of an [organism](/source/organism)), including genetic, physiologic, pathologic, and other aspects.{{cite journal |author=Aoki-Kinoshita KF |title=An Introduction to Bioinformatics for Glycomics Research |journal=PLOS Comput. Biol. |volume=4 |issue=5 |article-number=e1000075 |date=May 2008 |pmid=18516240 |pmc=2398734 |doi=10.1371/journal.pcbi.1000075 |last2=Lewitter |first2=Fran |editor1-last=Lewitter |editor1-first=Fran|bibcode=2008PLSCB...4E0075A |doi-access=free }}{{cite journal |author=Srivastava S |title=Move over proteomics, here comes glycomics |journal=J. Proteome Res. |volume=7 |issue=5 |page=1799 |date=May 2008 |pmid=18509903 |doi= 10.1021/pr083696k|doi-access= }} Glycomics "is the systematic study of all [glycan](/source/glycan) structures of a given cell type or organism" and is a subset of [glycobiology](/source/glycobiology).{{cite book |title=Essentials of Glycobiology |publisher=Cold Spring Harbor Laboratory Press |edition=2nd |year=2009 |isbn=978-0-87969-770-9 |url=http://www.cshlpress.com/default.tpl?action=full&--eqskudatarq=666}} The term glycomics is derived from the chemical prefix for sweetness or a sugar, "glyco-", and was formed to follow the ''[omics](/source/omics)'' naming convention established by [genomics](/source/genomics) (which deals with [gene](/source/gene)s) and [proteomics](/source/proteomics) (which deals with [protein](/source/protein)s). == 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](/source/glycoprotein)) or conjugated with lipids ([glycolipid](/source/glycolipid)s). *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.{{Cite journal|last1=Aizpurua-Olaizola|first1=O.|last2=Toraño|first2=J. Sastre|last3=Falcon-Perez|first3=J.M.|last4=Williams|first4=C.|last5=Reichardt|first5=N.|last6=Boons|first6=G.-J.|title=Mass spectrometry for glycan biomarker discovery|journal=TrAC Trends in Analytical Chemistry|volume=100|pages=7–14|doi=10.1016/j.trac.2017.12.015|year=2018|hdl=1874/364403 |hdl-access=free}} 68 building blocks (molecules for DNA, RNA and proteins; categories for lipids; types of sugar linkages for saccharides) provide the structural basis for the molecular choreography that constitutes the entire life of a cell. [DNA](/source/DNA) and [RNA](/source/RNA) have four building blocks each (the [nucleoside](/source/nucleoside)s or [nucleotide](/source/nucleotide)s). [Lipid](/source/Lipid)s are divided into eight categories based on [ketoacyl](/source/ketoacyl) and [isoprene](/source/isoprene). [Protein](/source/Protein)s have 20 (the [amino acid](/source/amino_acid)s). [Saccharide](/source/Saccharide_(disambiguation))s have 32 types of sugar linkages.[http://ucsdnews.ucsd.edu/newsrel/health/09-0868Molecules.asp ucsd news] article ''Do 68 Molecules Hold the Key to Understanding Disease?'' published September 3, 2008 While these building blocks can be attached only linearly for proteins and genes, they can be arranged in a branched array for saccharides, further increasing the degree of complexity. Add to this the complexity of the numerous proteins involved, not only as carriers of carbohydrate, the [glycoprotein](/source/glycoprotein)s, but proteins specifically involved in binding and reacting with carbohydrate: *Carbohydrate-specific [enzyme](/source/enzyme)s for synthesis, modulation, and degradation *[Lectin](/source/Lectin)s, carbohydrate-binding proteins of all sorts *[Receptors](/source/Receptor_(biochemistry)), 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: *[Glycoprotein](/source/Glycoprotein)s and Glycolipids found on the cell surface play a critical role in bacterial and viral [recognition](/source/Antigen_recognition). *They are involved in cellular [signaling pathway](/source/signaling_pathway)s and modulate cell function. *They are important in [innate immunity](/source/innate_immunity). *They determine [cancer](/source/cancer) development. *They orchestrate the cellular fate, inhibit [proliferation](/source/Cell_growth), regulate circulation and invasion. *They affect the stability and folding of [protein](/source/protein)s. *They affect the pathway and fate of [glycoprotein](/source/glycoprotein)s. *There are many glycan-specific diseases, often [hereditary diseases](/source/hereditary_diseases). There are important medical applications of aspects of glycomics: *[Lectin](/source/Lectin)s fractionate cells to avoid [graft-versus-host disease](/source/graft-versus-host_disease) in [hematopoietic stem cell transplantation](/source/hematopoietic_stem_cell_transplantation). *Activation and expansion of cytolytic [CD8](/source/CD8) [T cell](/source/T_cell)s in cancer treatment. Glycomics is particularly important in microbiology because glycans play diverse roles in bacterial physiology.{{cite book |last1=Reid |first1=Christopher W. |title=Bacterial glycomics: current research, technology, and applications |date=2012 |publisher=[Caister Academic Press](/source/Caister_Academic_Press) |location=Norfolk, UK |isbn=978-1-904455-95-0}} 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 ===High-resolution mass spectrometry (MS) and high-performance liquid chromatography (HPLC)=== The most commonly applied methods are [MS](/source/mass_spectrometry) and [HPLC](/source/high-performance_liquid_chromatography), in which the glycan part is cleaved either enzymatically or chemically from the target and subjected to analysis.{{cite journal |vauthors=Wada Y, Azadi P, Costello CE, etal |title=Comparison of the methods for profiling glycoprotein glycans—HUPO Human Disease Glycomics/Proteome Initiative multi-institutional study |journal=Glycobiology |volume=17 |issue=4 |pages=411–22 |date=April 2007 |pmid=17223647 |doi=10.1093/glycob/cwl086 |doi-access=free }} In case of glycolipids, they can be analyzed directly without separation of the lipid component. N-[glycans](/source/glycans) from glycoproteins are analyzed routinely by high-performance-liquid-chromatography (reversed phase, normal phase and ion exchange HPLC) after tagging the reducing end of the sugars with a fluorescent compound (reductive labeling).{{cite journal |vauthors=Hase S, Ikenaka T, Matsushima Y |title=Structure analyses of oligosaccharides by tagging of the reducing end sugars with a fluorescent compound |journal=Biochem. Biophys. Res. Commun. |volume=85 |issue=1 |pages=257–63 |date=November 1978 |pmid=743278 |doi=10.1016/S0006-291X(78)80037-0}} A large variety of different labels were introduced in the recent years, where 2-aminobenzamide (AB), anthranilic acid (AA), 2-aminopyridin (PA), 2-aminoacridone (AMAC) and 3-(acetylamino)-6-aminoacridine (AA-Ac) are just a few of them.{{cite journal |vauthors=Pabst M, Kolarich D, Pöltl G, etal |title=Comparison of fluorescent labels for oligosaccharides and introduction of a new postlabeling purification method |journal=Anal. Biochem. |volume=384 |issue=2 |pages=263–73 |date=January 2009 |pmid=18940176 |doi=10.1016/j.ab.2008.09.041 }} O-[glycans](/source/glycans) are usually analysed without any tags, due to the chemical release conditions preventing them to be labeled.{{cite journal |last1=Karlsson |first1=Niclas G. |last2=Jin |first2=Chunsheng |last3=Rojas-Macias |first3=Miguel A. |last4=Adamczyk |first4=Barbara |title=Next Generation O-Linked Glycomics |journal=Trends in Glycoscience and Glycotechnology |date=2017 |volume=299 |issue=166 |page=E35–E46 |doi=10.4052/tigg.1602.1E |doi-access=free }} Fractionated glycans from [high-performance liquid chromatography](/source/high-performance_liquid_chromatography) (HPLC) instruments can be further analyzed by [MALDI](/source/MALDI)-TOF-MS(MS) to get further information about structure and purity. Sometimes glycan pools are analyzed directly by [mass spectrometry](/source/mass_spectrometry) without prefractionation, although a discrimination between isobaric glycan structures is more challenging or even not always possible. Anyway, direct [MALDI](/source/MALDI)-TOF-MS analysis can lead to a fast and straightforward illustration of the glycan pool.{{cite journal |vauthors=Harvey DJ, Bateman RH, Bordoli RS, Tyldesley R |title=Ionisation and fragmentation of complex glycans with a quadrupole time-of-flight mass spectrometer fitted with a matrix-assisted laser desorption/ionisation ion source |journal=Rapid Commun. Mass Spectrom. |volume=14 |issue=22 |pages=2135–42 |year=2000 |pmid=11114021 |doi=10.1002/1097-0231(20001130)14:22<2135::AID-RCM143>3.0.CO;2-# |bibcode=2000RCMS...14.2135H }} 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](/source/Electrospray_ionization)) is frequently used for this application.{{cite journal|last1=Schulz|first1=BL|last2=Packer NH|first2=NH|last3=Karlsson|first3=NG|title=Small-scale analysis of O-linked oligosaccharides from glycoproteins and mucins separated by gel electrophoresis.|journal=Anal. Chem.|volume=74|issue=23|pages=6088–97|pmid=12498206|doi=10.1021/ac025890a|date=Dec 2002}}{{cite journal |vauthors=Pabst M, Bondili JS, Stadlmann J, Mach L, Altmann F |title=Mass plus retention time equals structure: a strategy for the analysis of N-glycans by carbon LC-ESI-MS and its application to fibrin N-glycans |journal=Anal. Chem. |volume=79 |issue=13 |pages=5051–7 |date=July 2007 |pmid=17539604 |doi=10.1021/ac070363i }}{{cite journal |vauthors=Ruhaak LR, Deelder AM, Wuhrer M |title=Oligosaccharide analysis by graphitized carbon liquid chromatography-mass spectrometry |journal=Anal Bioanal Chem |volume=394 |issue=1 |pages=163–74 |date=May 2009 |pmid=19247642 |doi=10.1007/s00216-009-2664-5 |s2cid=43431212 |doi-access=free }} ===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.{{cite journal |last1=Flowers |first1=SA |last2=Lane |first2=CS |last3=Karlsson |first3=NG |title=Deciphering Isomers with a Multiple Reaction Monitoring Method for the Complete Detectable ''O''-Glycan Repertoire of the Candidate Therapeutic, Lubricin. |journal=Analytical Chemistry |volume=91 |issue=15 |pages=9819–9827 |date=11 July 2019 |doi=10.1021/acs.analchem.9b01485 |pmid=31246420|s2cid=195759019 }}{{cite journal |vauthors=Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB | title = Glycans in the immune system and The Altered Glycan Theory of Autoimmunity | journal = J Autoimmun | volume = 57 | issue = 6 | pages = 1–13 | year = 2015 | pmid = 25578468 | doi = 10.1016/j.jaut.2014.12.002 | pmc=4340844}}{{Cite journal|last1=Flowers|first1=Sarah A.|last2=Ali|first2=Liaqat|last3=Lane|first3=Catherine S.|last4=Olin|first4=Magnus|last5=Karlsson|first5=Niclas G.|date=2013-04-01|title=Selected reaction monitoring to differentiate and relatively quantitate isomers of sulfated and unsulfated core 1 O-glycans from salivary MUC7 protein in rheumatoid arthritis|journal=Molecular & Cellular Proteomics|volume=12|issue=4|pages=921–931|doi=10.1074/mcp.M113.028878|doi-access=free |issn=1535-9484|pmc=3617339|pmid=23457413}} '''Table 1''': Advantages and disadvantages of mass spectrometry in glycan analysis {| class="wikitable" border="1" |- ! '''Advantages''' ! '''Disadvantages''' |- | *Applicable for small sample amounts (lower fmol range) *Useful for complex glycan mixtures (generation of a further analysis dimension). *Attachment sides can be analysed by tandem MS experiments (side specific glycan analysis). *Glycan sequencing by tandem MS experiments. | *Destructive method. *Need of a proper experimental design. |} ===Arrays=== Lectin and antibody arrays provide high-throughput screening of many samples containing glycans. This method uses either naturally occurring [lectins](/source/lectins) or artificial [monoclonal antibodies](/source/monoclonal_antibodies), where both are immobilized on a certain chip and incubated with a fluorescent glycoprotein sample. Glycan arrays, like that offered by the [Consortium for Functional Glycomics](/source/Consortium_for_Functional_Glycomics) and [http://www.zbiotech.com/ 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 [azide](/source/azide)-labeled sugars which can be reacted using the [Staudinger ligation](/source/Staudinger_ligation). This method has been used for in vitro and in vivo imaging of glycans. ===Tools for glycoproteins=== [X-ray crystallography](/source/X-ray_crystallography) and [nuclear magnetic resonance (NMR) spectroscopy](/source/Protein_nuclear_magnetic_resonance_spectroscopy) for complete structural analysis of complex glycans is a difficult and complex field. However, the structure of the binding site of numerous [lectin](/source/lectin)s, [enzyme](/source/enzyme)s and other carbohydrate-binding proteins has revealed a wide variety of the structural basis for glycome function. The purity of test samples have been obtained through [chromatography](/source/chromatography) ([affinity chromatography](/source/affinity_chromatography) etc.) and analytical [electrophoresis](/source/electrophoresis) ([PAGE (polyacrylamide electrophoresis)](/source/PAGE), [capillary electrophoresis](/source/capillary_electrophoresis), [affinity electrophoresis](/source/affinity_electrophoresis), etc.). == Software and databases == There are several online software and databases available for glycomics research. This includes: * [https://glycosmos.org/ GlyCosmos] * [https://glytoucan.org/ GlyTouCan] * [https://glygen.org/ GlyGen] * [GlycomeDB](/source/GlycomeDB) * [UniCarb-DB](/source/UniCarb-DB) ==See also== {{Portal|Biology|Medicine}} {{colbegin}} *[Cytomics](/source/Cytomics) *[Glycobiology](/source/Glycobiology) *[GlycomeDB](/source/GlycomeDB) *[UniCarb-DB](/source/UniCarb-DB) *[Carbohydrate Structure Database (CSDB)](/source/Carbohydrate_Structure_Database_(CSDB)) *[Glycoconjugate](/source/Glycoconjugate) *[Glyquest](/source/Glyquest) *[Interactomics](/source/Interactomics) *[Lipidomics](/source/Lipidomics) *[List of omics topics in biology](/source/List_of_omics_topics_in_biology) *[Metabolomics](/source/Metabolomics) *[Omics](/source/Omics) *[Proteomics](/source/Proteomics) *[systems biology](/source/systems_biology) *[Minimum Information Required About a Glycomics Experiment](/source/Minimum_Information_Required_About_a_Glycomics_Experiment) {{colend}} == References == {{reflist}} ==External links== *[https://web.archive.org/web/20180521104202/http://www.glycosciences.de/ glycosciences.de ] This site provides databases and bioinformatics tools for glycobiology and glycomics. *[http://www.glycome-db.org/About.action GlycomeDB], A carbohydrate structure [metadatabase](/source/metadatabase) *[https://web.archive.org/web/20180730105716/http://glycobase.nibrt.ie/ GlycoBase] A web HPLC/UPLC resource that contains elution positions expressed as glucose unit values. *[http://www.proglycan.com/ ProGlycAn] A short introduction to glycan analysis and a nomenclature for N-Glycans * {{cite web | author=Emanual Maverakis |display-authors=etal | title=Glycans in the immune system and The Altered Glycan Theory of Autoimmunity | url= http://ac.els-cdn.com/S0896841114001759/1-s2.0-S0896841114001759-main.pdf?_tid=fbc3820c-0881-11e5-b633-00000aacb362&acdnat=1433179187_223619b43246b42b6d0f8c696bf10ac7}} *[https://www.bioglyco.com/glycomics.html 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. {{Genomics}} Category:Glycomics Category:Omics Category:Carbohydrate chemistry --- Adapted from the Wikipedia article [Glycomics](https://en.wikipedia.org/wiki/Glycomics) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Glycomics?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.