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2021-04-06 demo

GlyGen Demo: New search tools and exploration of glycosylation sites.

Survey: https://docs.google.com/forms/d/e/1FAIpQLScNBNW0ToTgRYbxgn0JPC51WalGz4FLoYxgNnheB1H2TXcbEA/viewform

Recording: https://www.youtube.com/watch?v=Xw9AECStmQI

Questions from GlyGen Demo April 06, 2021

Q) Do you plan to integrate some tools that can also build the 3D structure of glycans? For example, Glycam sequences that can be used to model structure in Glycam web?

A) Yes, GlyGen is working with GLYCAM resources to generate 3D structures for glycan and glycoproteins using the GLYCAM 3D structure visualizer and builder.

Q) Can you elaborate on the utility of proteoglycans? (question will be shortened)

A) GlyGen stores both the protein and glycan portion of proteoglycans. However, digital data assigning specific proteoglycan glycans to specific sites on the proteins are sparse. You can look at Aggregan as an example (UniProt Accession P16112). There are several O-linked sites reported but none of the reports provides a specific GAG attached to these sites. From other sources we did retrieve GAG structures but without a protein annotation. These GAGs can best be found by using the Glycan search ⇒ Composition search and allow any monosaccharide but require at least one HexA. The result will be this list that contains many GAG structures. These structures can either contain the Xylose core (e.g. GlyTouCan ID: G26915TH) or consist purely of the polysaccharide part with one (e.g. GlyTouCan ID: G09687RJ) or multiple polymer units (e.g. GlyTouCan ID: G84530VQ) with and without sulfation pattern. We are currently working to support the classification of GAG glycans in the GlycoMotif and GlycanData projects to make these glycans easier to find.

Q) The tools you showed can be used with proteoglycans and glycosaminoglycans?

A) See answer above.

Q) What organisms do you plan to include in future updates?

A) We are actively working towards incorporating Drosophila as our next organism. We are also evaluating other model organisms, as well as pathogenic microbes and viruses.  GlyGen would appreciate input regarding what organisms would be most useful for investigators.  Best organisms should be those that would be as broadly impactful as possible and also have an existing set of data that is rich and that can be connected to other resources in meaningful ways (mutants, functional analysis, fully annotated genomes, rich biochemical data, etc.).

Q) Will GlyGen has its own curation of glycoenzymes to glycosylation pathways (N-linked, O-linked GSL GAG), or will this information be cross-referenced from other databases?

A) GlyGen has been curating and maintaining a set of glycoenzymes (glycosyltransferases and glycohydrolases) for human, mouse, and rat organisms. Eg. - here is a list of Human Glycosyltransferases. Whereas the information for glycosylation pathways for such glycoenzymes is being integrated from resources such as Reactome, Rhea, KEGG, etc. From the available knowledge and expertise, GlyGen has been developing an interactive tool ‘Sandbox’ that will allow users to explore glycan biosynthetic pathways. Check out the current version of Sandbox.

Q) What are your upcoming plans for new tools?

A) In the coming months, we plan to develop tools such as batch retrieval tool that will allow batch retrieval of glycans and proteins, BLAST to search for glycopeptides and glycoproteins, basket tool to add selected glycans and proteins for further exploration, filter options for search results, glycan export to support MS software tools such as GRITS Toolbox and Byonic, advanced composition search tool with more options to search for glycan compositions, (glycan sequence converter?), etc. We also plan to add more functionalities and new data types (e.g. Phosphorylation and enzyme annotation) and enhance the existing developed tools.

Q) Can the DB be used to investigate the use of GP as adjuvants?

A) GlyGen does not currently incorporate data regarding the use of glycoproteins as orthogonal reagents for purposes of adjuvanting or other applications.  The data in GlyGen is currently focused on the primary structure and functions of glycans and glycoproteins.  It is possible, however, that some structural information has been derived from studies that investigated the use of glycoproteins in vaccines, either as an immunogen or as an additive.  Interestingly, however, if you type the word “adjuvant” into the global search query (upper right hand on the home page), the search returns 35 proteins.  The first on this list is MUC1.  If you click on this result and look in the “Function” section of the protein details page, you will find a statement and a reference to the following:  

“Dendritic Cell-based Immunotherapy Pulsed With Wilms Tumor 1 Peptide and Mucin 1 as an Adjuvant Therapy for Pancreatic Ductal Adenocarcinoma After Curative Resection: A Phase I/IIa Clinical Trial.”

Further exploration of other search results may provide you with additional examples that are relevant to your interests.  

Q) Are there functions to filter glycans with exact structures?  Some structures have ambiguous structures.

A) The GlyGen’s Super Search option can be used to filter fully defined/determined glycans. In the Super Search, select Glycan property and select a fully defined option and search to get a list of fully defined glycans. Alternatively, you can access the dataset that contains fully defined/determined structures in GlyGen. We are also working on a feature to filter glycans from search result pages. This feature will be available with the next GlyGen release this summer.

Q) Are you planning to expand the data for fungi and bacteria?

A) We are exploring the possibility of integrating the data for plants, fungi, and bacteria but given the complexity involved in the integration (selection of proteome, data model) such integration requires further evaluation, careful planning, and engaging with experts in these areas of glycobiology.


Q) Does GlyGen include mucin-type O-glycans? And what about microbial glycosylation? Is this something you are looking to expand to in the future? (Question will be shortened)

A) GlyGen does include mucin-type O-glycans and can be searched and explored through the glycan advanced search page by selecting Glycan type as O-linked and then by selecting the appropriate Glycan subtype. Alternatively, you can perform the search through Super Search by selecting the option O-linked from the Glycan class and choose the appropriate subclass from the Glycan subclass option. See the above answer regarding bacterial glycans.

Q) When searching for proteins or sites that have a particular glycan, how restrictive are the requirements for linkage isomers? Does searching for a specific linkage for fucose or sialic acid include results with unknown linkage, or does the search only return glycans with those specific linkages?

A) The association between a protein site and glycan is represented by the GlyGen/GlyTouCan accession of the glycan that precisely captures the known and unknown status of each linkage as supported by documentation in the literature sources. However, the GNOme Structure Browser applet (called Related Glycans on Glycan pages) makes it possible to explore related glycan accessions by subsumption, and/or to place all subsuming (ancestor accessions) or subsumed (descendant accession) in the copy-and-paste clipboard. These accessions can be used with the Advanced Glycan Search. Some GlyGen data-types and searches are subsumption-aware and will apply this logic automatically, though support for this is still developing.

Q) What are the advantages of the GlyGen resource in comparison to the other glycan/carbohydrate databases, e.g., GlyTouCan?

A) GlyTouCan is a resource for registering glycans and a repository for storing glycans structures, similar to NCBI GenBank that is a repository for nucleotide sequences. Whereas resources like GlyGen are data dissemination knowledge bases that integrate diverse types of data from multiple data sources and harmonize this data for further exploration. GlyGen not only contains knowledge about glycans but also contains extensive knowledge about genes, glycoproteins, glycoenzymes. GlyGen collaborates with GlyTouCan, as well as with GlyCosmos and GlyConnect, to harmonize data across international glycoinformatics efforts. GlyGen is meant as a bridge between different domains and databases. While GlyTouCan has glycan information it has no information on the attached proteins. From the protein perspective, UniProt is THE information source for proteins and while it has glycosylation sites it does not have the actual glycan structures and their associated information. Resources such as UniCarbKB and GlyConnect also have glycan-protein attachment information. GlyGen brings this all together. Integrating data from glycoproteomics resources (UniCarbKB, GlyConnect) into a single database but adding information from other resources as well (GlyTouCan and PubChem for Glycans, UniProt and PDB for proteins, etc.). In addition, GlyGen also links back to the primary databases and literature sources that the data originates from allowing for an in-depth exploration of glycans and proteins.

Q) Are all the glycan information in GlyGen based on the published results?

A) Not all glycans integrated into GlyGen have associated literature evidence. Although, if the glycan has been assigned to a site of glycosylation on a protein, a link to the literature evidence is presented. The publication section on Glycan detail pages lists the literature evidence when available. Most glycan information, especially the information supplied by third-party data providers, is evidence tagged with the source of the information. Some of these data providers provide their annotations on the basis of publications and include information about the publication with their annotations, these are displayed as badges alongside the data-provider badges.