Subgroup goals
Michael Tiemeyer
Saturday, 05 July 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 July 2008 02:13 UTC
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For those of you attending the CFG meeting prior to the Society for Glycobiology meeting this fall in Ft. Worth, TX, each subgroup will be holding a meeting of its members. Are there topics that you think would be worth putting on a discussion agenda for that meeting? Remember, we can make of this forum anything we want, so be creative. Glycopoetry slam, perhaps?
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The administrators of the various CFG Subgroup forums are currently trying to figure out the best way to allow the lab members of CFG investigators to join into the discussions. Are you interested in opening this forum to the input of our lab members? Would you be willing to designate a single account for all of your lab members? Or, would you prefer to swing the doors wide-open?
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Anonymous
I have recently joined the glycomics field and have little knowledge of it. We have unexpectedly found evidence that glycosylation is defective in animal and cell models of the disease we are studying and that this is likely a key event in the pathogenesis. I am eager to characterize the defects in glycosylation using the samples we have already collected. This was the primary reason I joined CFG several months ago; and my request is yet to be considered.
I am afraid I do not know how to most efficiently use the CFG Core resources to move forward with our exciting findings. I would appreciate any advice and welcome any collaboration.
Anna Gukovskaya, Ph.D.
Adjunct Professor, David Geffen School of Medicine,
University of California at Los Angeles.
Co-Director, Pancreatic Research Group
VA Greater Los Angeles Healthcare System.West Los Angeles VA Healthcare Center
11301 Wilshire Blvd, Blg 258, Rm 340
Los Angeles, CA 90073, USA.
Tel: (310) 478-3711 x41525
Fax: 310-268-4578
E-mail: agukovsk@ucla.edu -
Hi Anna,
I am sure I speak for Mike T. as well when I say pick up the phone and give us a call at the Complex Carbohydrate Research Center…we would be happy to talk with you about your project and either help or guide you to who we think could best help you.Cheers,
Lance Wells
(706) 542-7806 -
Participation in this Network is now open to your lab members!! A single account must first be established for use by all lab members. Just have someone in your group (or you) apply to open an account for your group by following these instructions:
To join the Network forum for our subgroup…
- Go to http://network.nature.com/
- Register and create a login using the name “X Lab”, where X = PI’s name. You will have to select a single individual’s e-mail address (other than the PI’s) to open the account.
- Fill out profile information as desired.
- Go to the CFG group page at http://network.nature.com/group/cfg
- Click “join this group” and wait for the administrator to accept your request
- Follow the links in the CFG group to join your subgroup(s)
- Start posting to the forums
- The identity of the post will be from whatever Profile Information is provided, like “X Lab.” If an individual poster wants to identify themselves, they should do so in the body of their posting.
By opening participation to lab members, we hope to enliven our discussions and generate a forum of considerable practical utility.
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The first face-to-face Subgroup Meeting will be from 3:45 – 4:40, November 12 during the CFG Satellite meeting in Ft. Worth. I hope that as many of you can attend as possible. If you have specific issues that you would like the subgroup to discuss, please send them along to me and I’ll add them to the agenda. It would be great if we could post some of these agenda items on this site before the meeting so that we all have a chance to think about them.
Among the most important agenda items might be to discuss how we would like to see CFG resources directed for the coming years. What parts of the CFG have been most useful for us and should they be “evergreened” beyond the end of the CFG? How can this be accomplished? Can we identify some focused analytical projects that could be accomplished in the next two to three years by the combined efforts of our individual laboratories? What CFG resources would be required to accomplish such projects?
NIGMS has set aside a reasonable amount of funding for focused CFG Subgroup meetings in the coming years. Is there an aspect of Analytical Glycomics that might benefit from such a meeting? Warren Workshop items come to mind. Also, a joint meeting with Subgroup 10 (Bioinformatics) might be profitable.
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Thanks to everybody that participated in the first face-to-face subgroup meeting in Ft. Worth. Pasted below is the summary of the meeting as submitted to the steering committee and to NIGMS. I hope that it captures the content of our discussion. Please feel free to add any additional comments. I’ve started two new discussion boards. The purpose of the first is to build a wishlist of glycan standards. The purpose of the second is to discuss possible topics for a joint subgroup meeting in the spring. Both of these items are addressed in the summary below.
Also, remember that you can set-up a mechanism for the people in your lab to contribute to our on-going discussions here. If you look down to my contribution to this discussion board on 10/12/08, you will see instructions for setting-up lab accounts. Please encourage participation!!
Now, the report:
Subgroup #7: Analytical Glycomics
The first meeting of subgroup #7, Analytical Glycomics, was well attended and characterized by a reassuring level of consensus on important issues. A standing-room-only crowd of slightly more than 50 people discussed the following general topics:
1. The purpose of the Subgroup
2. Projects that leverage the strengths of Subgroup members to address the major goals of the CFG
3. Well-justified resources to assist in these projects over the next three years
4. Workshops of high value to Subgroup membersIn regard to these topics, the discussions highlighted the following issues:
The purpose of the Subgroup—A consensus emerged that the Subgroup could serve a useful function as a conduit for information and data exchange as collaborative projects are identified and developed. Several specific areas were discussed in which Subgroup communication might prove useful. There was broad agreement among the Investigators that the Nature Network is still not on the radar and that its value would likely increase as the user base is expanded to include lab members. To this end, Investigator’s were reminded of the mechanism to set-up lab accounts and that further instruction can be found on the Nature Network. Other specific contexts in which the Nature Network was thought to be of potential use were discussed and are highlighted below, where appropriate.
The efforts of other groups of analytical glycomicists were discussed in relation to the role of the Subgroup. In particular, the Subgroup wishes to pursue efforts that are complementary to those of Investigators who have already begun to address standardization of data interpretation, especially those that have grown out of the Warren Workshops. Joseph Zaia spoke on behalf of these efforts and many Subgroup members are an integral part of those ongoing discussions. As the efforts of that working group expand, Subgroup #7 will work to provide an open forum for discussion of results and for input from the community. It is anticipated that the Nature Network can facilitate these discussions.
Potential Subgroup projects—Two projects were discussed.
1. Prioritize and obtain glycan standards for characterization of mass spectrometric approaches. Through Subgroup communication (Nature Network), a prioritized wishlist of glycan structures would be developed. These standards would be used to address questions related to quantitative and predictive aspects of mass spectrometry.
a. What are the molar response factors for a broad range of permethylated glycan structural types in the hands of appropriately experienced analysts using the range of currently available instrumentation?
b. How quantitative is MS and MSn analysis?
c. Can diagnostic and broadly accessible fragmentation schemes be developed based on well-characterized standards?
d. What sort of metadata should be captured to maximize the value of standard analysis? A consensus of the subgroup was that NMR and compositional analysis is probably the minimally sufficient characterization. Further thought should be given to capturing relevant instrumentation conditions and settings.2. Assess the validity of interpreting lectin/antibody binding to cells or tissues with regard to the content of glycan and the specificity of the probe. Several Subgroup members emphatically pointed out that the access of most laboratories to mass spectrometry resources is insufficient to make MS a viable, routine experimental tool. A large cohort of glycobiologists will continue to rely on antibody and lectin probes to assess the glycan composition of cells and tissues. In many cases, the sensitivity of these probes is superlative. However, relatively few direct comparisons have been made between the results of probe binding and of glycan analysis.
a. Subgroup members would undertake lectin/antibody binding studies to cells that have already had (or are scheduled to have) their glycan compositions determined by Core C.
b. The selected probes or antibodies would come from those that have already been screened on the CFG Glycan Array or would be submitted for screening on the Array.
c. This project leverages the developed datasets of the CFG Glycan Array and the Glycan Analysis Cores. The correlation of unexpected hits and alternative binding structures with the detection of minor glycan components could provide a robust threshold for claiming the specificity of binding probes.
d. Careful thought should be given to conditions and to what metadata is most appropriate for capture (cell culture conditions, lectin source and concentration, inhibitory hapten concentration, multiple lectin concentrations, congruence between cell binding and array binding conditions, etc.)Well-justified resources—Both in the Subgroup meeting and also in the responses of Subgroup members to the CFG survey, the availability of glycan standards stands out as the single most-identified need. Subgroup members indicated that the Nature Network would be a good place to begin discussions regarding the prioritization of standards and the commercial availability of compounds. The Consortium’s efforts towards generating standards were also discussed. It was strongly expressed that standards should have an intact reducing terminal to most closely match the types of materials generated by Investigators. Therefore, standards generated for the Glycan Array are not optimal. Although the Subgroup was informed that the CFG is currently initiating the generation of intact glycan standards, members indicated that we should take advantage of those glycans that may be immediately available in the community or from commercial sources. Therefore, subgroup members will compile a listing of available glycans and their cost from a broad range of sources. It is anticipated that many glycans from commercial sources will require characterization (see above). The resources needed to obtain and characterize glycan standards would be extremely valuable and are well-justified based on the need for the community to develop consensus on the interpretation and quantifiability of MS-based analysis.
Subgroup meetings—Analytical Glycomics Subgroup members were strongly in favor of a joint meeting with the Bioinformatics Subgroup. It was felt that the major bottleneck in glycan analysis is not sample handling or data acquisition, but rather data interpretation. While programs such as Cartoonist and Glycoworkbench have begun to make important inroads into automating MS analysis, a significant level of manual effort and expertise is still required for full characterization of glycan profiles. Furthermore, significant volumes of glycomic data are being generated but the best course for correlating glycan composition with other “-omic” based analysis, such as transcriptomics and proteomics, is still murky. By bringing together Glycomic Investigators with Bioinformaticists, each may be able to inform the other on best practices and new synergistic approaches. Furthermore, several Investigators expressed a desire to get things right, from the outset, in building broadly useful glycomics databases, avoiding the mistakes made in early proteomics databases. It was noted that the Warren Workshop meets biannually and 2009 is an off-year. Therefore, by holding a joint meeting in Spring 2009 (April was suggested as a possibility), the Analytical Glycomics and the Bioinformatics Subgroups can complement rather than compete with the efforts of the Warren Workshop. Subgroup members preferred a small meeting size (30-50 people maximum) and the NIH venue was thought to be most valuable.
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The Steering Committee of the CFG, in response to a request from NIGMS, has asked each subgroup to define specific milestones for the next 8 months. I have tried to harvest achievable milestones from the discussions that we had in our face-to-face meeting in Ft. Worth. Your comments are most welcome.
Analytical Glycomics (Subgroup #7) Proposed Milestones (for completion by end of year 8—Aug 31, 2009)
1. Convene a joint subgroup meeting with Bioinformatics Subgroup (#10) by late spring.
2. Develop consensus on criteria for reporting glycan structural characterization in the literature and for incorporation into databases (with Subgroup #10).
3. Define goals and opportunities for mining relationships between glycan structural datasets that have already been generated by the CFG.
4. Develop list of 50 oligosaccharide standards (intact reducing terminus) that are desired by the community and are most likely to facilitate advances in MS methodologies.
5. Identify sources for these standards, with special reference to the efforts of the CFG synthetic core.
6. Develop consensus on necessary characterization and best use of identified standards.The Steering Committee will be reviewing these milestones in the very near future. Any input that would allow us to shape these goals in a way that maximally benefits the community would be most appreciated.
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The goals sound good to me. Does it make sense to expand #3 beyond CFG generated datasets? Perhaps the subgroup could investigate how to expand the set of publicly available datasets.
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David (and anybody else out there):
I agree! We should be looking at how the CFG data fits with data acquired anywhere and everywhere else. We should look across the CFG data for trends and highlights of interest and we should reference these to anyother datasets that are accessible and searchable. With Bioinformatics, perhaps we can figure out how to do this.
These goals/milestones are a draft at this point and will be finalized (at least as far as NIGMS is concerned by early February. I will certainly expand goal #3 to reflect your input.
THANKS FOR YOUR POST. It has been quite lonely here for a long time.
Cheers,
MikeT
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