Molecular Omics View Article Online EDITORIAL View Journal | View Issue Glycomics & Glycoproteomics: From Analytics to Function Cite this: Mol. Omics, 2021, 17,8 Morten Thaysen-Andersen, †ab Daniel Kolarich †cd and Nicolle H. Packer †*abcd DOI: 10.1039/d0mo90019b rsc.li/molomics ‘‘In analogy to the current situation in life sciences. As exemplified by papers pub- Donald et al., DOI: 10.1039/C9MO00168A) Cosmology, glycans can be considered as lished in this themed issue in Molecular also contribute to an ever-expanding analy- the ‘‘dark matter’’ of the biological uni- Omics ‘‘Glycomics & Glycoproteomics: tical toolbox that now allows scientists to verse: a major and critical component that From Analytics to Function’’, studies that explore not only the structure but also the has yet to be fully incorporated into the concertedly apply two or more glyco-centric biosynthesis and function of glycans and ‘‘standard model’’ of biology.’’ ‘omics techniques to uncover new mechan- glycoproteins. Ajit Varki and Stuart Kornfeld1 isms in various research areas in glycobiol- The field has for years recognised that ogy such as pathogen–host interactions no single technology can provide an in- (Cain et al., DOI: 10.1039/D0MO00032A; depth, often overlooked, understanding Outlining the topic and Mule et al., DOI: 10.1039/D0MO00043D; of the compositional, structural and its importance Delannoy et al., DOI: 10.1039/C9MO001 functional heterogeneity inherently asso- 73E; Mthembu et al., DOI: 10.1039/ ciated with protein glycosylation. None- Glycomics and glycoproteomics define C9MO00175A) cancer and biomarkers theless, integration of glycomics and Published on 09 December 2020. Downloaded 9/23/2021 11:22:50 PM. powerful technologies that help scientists (Chandler et al., DOI: 10.1039/D0MO000 glycoproteomics with the many inter- to capture this biological ‘‘dark matter’’ 09D; Acharya et al., DOI: 10.1039/C9MO00 facing ‘omics disciplines has only com- and study all glycans and glycoproteins 061E) and embryogenesis (Qu et al.,DOI: menced recently. Multifaceted analytical expressed by cells, tissues or organisms at 10.1039/D0MO00005A), are becoming com- strategies and the integration of glyco- a given time, space and condition.2–4 mon in the literature. This themed issue mics and glycoproteomics with proteo- While both glycomics and glycopro- also illustrates that mass spectro- mics, transcriptomics, metabolomics teomics methods have existed for several metry-based glycoproteomics studies often and genomics are critical to dive deeper years,5–8 key advances in the separation use multiple orthogonal fragmen- into the immensely complex and sciences, mass spectrometry and infor- tation schemes to produce complementary dynamic glycoproteome, the underpin- matics have recently allowed for a more glycan structural information to aid glyco- ning glycosylation machinery and their complete implementation and integration peptide characterisation at scale, with sen- effects on cellular activity. Glycobiology, of glycomics and glycoproteomics in the sitivity, speed and accuracy (Pap et al.,DOI: arguably more than other biological 10.1039/C9MO00160C; Chalkley et al.,DOI: research areas, benefits from the synergy 10.1039/C9MO00178F). Other new technol- that can be accessed using multi-omics a Department of Molecular Sciences, Macquarie ogy improvements (Cordina et al.,DOI:10. approaches as, for example, demon- University, Sydney, NSW, 2109, Australia. strated in ‘‘glycomics-assisted glycoproteo- E-mail: [email protected] 1039/C9MO00181F; Zhang et al.,DOI:10. 9–11 b Biomolecular Discovery Research Centre, Macquarie 1039/C9MO00180H; Sethi et al., DOI: 10. mics’’ studies. In such studies, the University, Sydney, NSW, 2109, Australia 1039/D0MO00019A), informatics advance- glycomics data not only provide essential c Institute for Glycomics, Griffith University, Southport, ments (Chalkley et al., DOI: 10.1039/ information on the fine detail of the QLD, 4222, Australia C9MO00178F; Uh et al., DOI: 10.1039/ attached glycan structures and define d ARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW, C9MO00174C; Phung et al., DOI: 10.1039/ the boundaries of the glycome, but also 2019, Australia C9MO00125E) and pathway analyses (del enable more effective characterisation of † Contributed equally. Solar et al., DOI: 10.1039/D0MO00023J; the accompanying glycoproteomics data 8 | Mol. Omics,2021,17,8À10 This journal is The Royal Society of Chemistry 2021 View Article Online Editorial Molecular Omics and give insights into the role of glycans glycoproteins.23–25 The development of to treat, cure and ultimately prevent in protein function. glycobioinformatics tools and curated disease and new biomarkers to diagnose The body of research papers compiled databases, together with the implemen- and prognose diseases, are ongoing.33–35 in this themed issue and elsewhere tation of standardized reporting guide- Not to be forgotten in the future, of clearly shows that glycomics and glyco- lines such as MIRAGE (Minimum course, is that glycomics does not only proteomics have matured considerably Information Required For a Glycomics apply to the structure and function of over the past years. As the wider scientific Experiment)26–29 (https://www.beilstein- proteins, but also refers to the character- community increasingly accesses these institut.de/en/projects/mirage/), to cope isation of glycans that are found attached technologies, and the workflows and with these data are essential for the to lipid anchors or found as free glycans, data collection, interpretation, reporting continued penetration of glycobiology proteoglycans, bacterial lipopolysacchar- and sharing are being streamlined, we into the many streams of life sciences. ides and peptidoglycans. At this time, the are beginning to unlock the real poten- The agreed implementation of a com- technologies for the analysis of these tial of glycomics and glycoproteomics to mon ‘‘glyco-language’’ via the ‘‘Symbol molecules are in their infancy, and are generate new insights into how the het- Nomenclature for Glycans (SNFG)’’30,31 practised by few laboratories world-wide, erogeneous glycosylation of proteins is together with the assignment of unique but must be taken into consideration as involved in so many biological processes. accession numbers to the glycan struc- we come to realise that multi-omics ana- tures (https://glytoucan.org/) has started lyses must be addressed across the entire to unify and facilitate the depiction and breadth of molecular sciences if we are to Future directions of the data sharing of complex biomolecular understand the complex systems that are field structures across the chemical and bio- biology. logical sciences. At present, the mass spectrometric tech- Despite this progress, the most com- nologies, when applied to mixtures of mon response of scientists to the ques- References intact glycopeptides, mostly assign the tion as to why they have not explored the monosaccharide compositions of glycans glycobiology of their research question at 1 A. Varki, et al.,inEssentials of Glyco- to peptides, and only in favourable cases hand has been that it is ‘‘too hard’’ – this biology, ed. A. Varki, R. D. Cummings, to discrete sites. However, more intricate reluctance can only be addressed by the J. D. Esko, P. Stanley, G. W. Hart, structural features of glycans are often availability of user friendly methods, M. Aebi, A. G. Darvill, T. Kinoshita, required to understand the effect of gly- software and accurate knowledge bases N. H. Packer, J. H. Prestegard, cosylation on protein function in such of glycobiological information. This R. L. Schnaar and P. H. Seeberger, areas as cellular interactions, protein information needs to be not only that Cold Spring Harbor Laboratory Press, cleavage, immune recognition and in acquired by the technologies of glyco- Cold Spring Harbor (NY), 3rd edn, biomarker discovery. Technologies that mics and glycoproteomics, but the seam- 2015–2017. Published on 09 December 2020. Downloaded 9/23/2021 11:22:50 PM. can uncover the heterogeneity of detailed less integration of such datasets with 2 M. Thaysen-Andersen, N. H. Packer structures decorating each protein site information delivered by well-estab- and B. L. Schulz, Maturing Glycopro- remain at this time a ‘‘holy grail’’ of lished genomics, transcriptomics, pro- teomics Technologies Provide glycobiology. Excitingly, innovative devel- teomics, metabolomics and/or lipido- Unique Structural Insights into the opments in ‘‘structure-focused glycopro- mics technologies for an integrated and N-glycoproteome and Its Regulation teomics’’ employing, for example, diagno- holistic understanding of cellular biology in Health and Disease, Mol. Cell. Pro- stic tandem mass spectrometry fragment in health and disease, such as has now teomics, 2016, 15(6), 1773–1790. ions,12–14 sequential exoglycosidase begun with the international glycoinfor- 3 K. Alagesan, A. Everest-Dass and digestions on glycopeptides,15,16 differ- matics initiatives of GlyConnect (https:// D. Kolarich, Isomeric Separation and ential liquid chromatography and ion glyconnect.expasy.org/), Glygen (https:// Characterisation of Glycoconjugates, mobility based retention,17–21 and glygen.org/) and GlyCosmos (https://gly Adv. Exp. Med. Biol., 2018, 1104, linkage-specific derivatisation of glyco- cosmos.org/) under the collaborative Gly- 77–99. peptides,22 to annotate certain glycan Space Alliance.32 4 R. Raghunathan, et al., Proteomics, structural features