CFG Subgroup: Analytical glycomics group: topic

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Subgroup goals

Michael Tiemeyer

Saturday, 05 Jul 2008 17:10 UTC

How can we use this network most effectively? At the outset, I thought it would be useful to think collectively about this question. To get things going, I’ll make a few suggestions for topic categories (somewhat overlapping in nature) that might be fruitful to explore. I apologize for being wordy here, I hope that our subgroup interactions can be more in the spirit of conversation rather than long-winded discourse, but we need to start somewhere.

Topic 1. Wouldn’t it be nice to have…

The thing that you are thinking that you need right now may already be under development by somebody else. And, we all know how frequently it happens that somebody is building a tool that will eventually be of great value but it’s development would be enhanced by real world trials or by application of real world data. A totally (?) fictitious example:

Post 1: I’ve got hundreds/thousands of glycan fragmentation profiles showing minor fragment ions that I can’t assign. It sure would be great to have a predictive program that gives me a list of realistic options.

Post 2: I’ve got a new applet that can take your list of fragments and present candidate structures with annotated fragmentation but need some real data to eliminate unlikely cross-ring cleavages.

Topic 2. We have an essential need for…..

We all face similar challenges in our glycomics efforts. A major one relates to quantification of glycans in complex mixtures. For most of the high-resolution, high-sensitivity approaches (ie: MS-based) currently in use, we are in dire need of appropriate standards. To the extent that we can come-up with a consensus or a list of ranked priorities, perhaps we can stimulate efforts to generate large quantities of synthetic or semi-synthetic standards. Or, perhaps we can identify the best uses for limited amounts of standards that would have the broadest impact. I’m sure we all have a list of dearly needed essentials that could benefit from some outside input.

Topic 3. High priority, breakthrough technologies…

For the most part, I don’t think that we really understand the full limitations of our current glycomics technologies. We know what we see, but we don’t always know what we’re missing. The extent of our ignorance is also dependent on glycan class (N-linked, O-linked, glycosphingolipid). Usually, increases in instrument sensitivity initiate the discovery of new glycans. Placing specific glycans onto specific peptides with high throughput and high sensitivity is a frontier that also cries out for new technological strides. What do we want from the new technologies? Where are the best chances for breakthrough?

Topic 4. High priority, breakthrough opportunities….

By opportunities, I mean biological targets that fit within (or fall outside) the purview of the CFG to “define the paradigms by which glycan binding proteins mediate cell communication.” These targets don’t necessarily have to be areas of personal research interest but could be a revelation that hits while reading outside our areas of comfort. Glycobiology, in general, has certainly benefited by extending into new areas.

As your “subgroup leader/moderator” I welcome all topics of general interest to analytical glycomics and promise not to be so wordy in the future. I hope that we can avoid becoming too balkanized (glycoprotein, glycolipid, GAG, mucinous, etc.) since the problems that limit our progress are probably more common to all of us than specific to our glycans of interest. And finally, I hope we can all find a way to use this network to our advantage and to our enjoyment.

Updated 08 Jul 2008 02:13 UTC

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    • in my view, one of the major obstacles to the realization of the goals of high-throughput glycomics has been and still is the lack of a comprehensive database of glycan structures found in various organisms and tissues. The CFG databases provide a great resource for the study of human and murine samples, but are still far from complete and also neglect other organisms which could be important for disease research.

      Without a comprehensive structure database the development of bioinformatics tools for the automated analysis of mass spectrometry data will always be limited. The currently available annotation tools can be generic but semi-automatic such as the GlycoWorkbench or completely automatic but limited to human structures (for which already a consistent body of knowledge is available) such as Cartoonist from David Goldberg. An integration of these two softwares could represent a step forward in the development of such tools, but their extension to other organisms and instrumentations requires the translation of the knowledge that is available only as publications into database records.

      The creation of a comprehensive structure database is both a matter of developing a suitable software infrastructure and of collecting the information from the various sources (literature and new research). The EUROCarbDB initiative is working on the first task and is already providing an example of what such database could be. The EUROCarbDB project has also developed the resources needed to collect the structural data, however for such a big task the involvement of the community is fundamental.

      I think the time is mature to reach this objective, but what is missing now are the resources to organize, coordinate and facilitate this community effort, and to maintain the database on a long term perspective.

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