Where do we go from here? #565
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Hi @cdsouthan. A lot to address in a single post, but thanks for starting. Briefly: My move will not result in any major changes to how OSM works - we are online and a decentralised group by design. My aim (hopefully our aim) is for OSM to grow - we must if we are to bias the odds in our favour of progressing a molecule to preclinical. Pursuing major funding will be a priority for me. In the short term I will be able to put a chemistry postdoc on OSM for 2 years in London (advert coming soon). This person will work with Ed, Marat and Tha, who will work on their OSM-related PhD research in Sydney, hopefully with extended research stays in London. Besides we (as a group) seeking more support I am hoping that others will take a leaf out of @holeung 's book and pursue funding independently towards OSM projects, where OSM acts as a big in-kind resource that adds value to the direct grant funding. S4 has continued promise, particularly if the Pfizer compound displays potency and improved solubility. There are several other candidates vs ATP4 in development, absolutely, but none are yet there (this could change!) There is work remaining (and a paper) on predictive activity modeling with Kiaran Kirk and the refinement of the competition entries - coming soon once Kiaran's paper is accepted. If Series 3 continues to show promise, then there is work to be done there too. But there can always be Series 5, 6 and so on if people want to argue the case and take on the responsibility of posting initial data. Having several series to pursue will greatly improve the chances of core funding for the platform in the coming years particularly if we prioritise novel MoA. There is a huge amount to do on improving the ways we work - the difficulty of securing resources for this is one of the reasons platform (as opposed to project-specific) funding is so important. There is also a lot to do on crowdsourcing synthesis, where we need dedicated resources for coordinating student teams (Alice in Sydney and a new contact at my Alma Mater, Queen Mary, for example). (Re the repository - Sydney and UCL both have robust repositories, as do most universities nowadays, but are you thinking of contributors who are not part of such institutions and who are regularly generating data? It might be easier to enable guest rights to existing repos?) Lots to discuss here (please keep going below) but, briefly, upshot is: i) OSM needs to grow if we want to demonstrate that an open source-derived compound can progress, ii) several of my students in Sydney (plus new postdoc in London) will continue their research as normal, iii) we need as a group to be submitting significant applications for support for our work in the coming 12 months. |
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@mattodd and @cdsouthan - I added to this open thread since it mentions the S4 paper. Using the 'Time & Date' link Matt mentioned in the Google Docs chat, might I suggest the below listed times for a meeting concerning the S4 paper:
I am certainly amenable to changes. Thanks. |
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Should be OK @mattodd @MedChemProf - but can we get @danaklug who I think has done the lions share of drafting so far? Cheers |
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Would prefer the earlier time if people can make it @danaklug @edwintse . |
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Proposed times are fine by me! |
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Thanks. I can send out a Zoom invite info here for anyone to join in if they would like. Is that acceptable? Or would you suggest another online meeting platform. @cdsouthan @danaklug @mattodd @edwintse |
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Yes, let's Zoom it. |
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@cdsouthan @mattodd @danaklug @edwintse Topic: OSM Series 4 Meeting Join Zoom Meeting Meeting ID: 318 791 8869 Dial by your location Join by SIP Join by H.323 |
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I will be there! |
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Apologies, had a clash this morning. Look forward to plans in dues course
…On Fri, Oct 16, 2020 at 7:38 PM Chase Smith ***@***.***> wrote:
Thanks. I can send out a Zoom invite info here for anyone to join in if
they would like. Is that acceptable? Or would you suggest another online
meeting platform. @cdsouthan <https://github.com/cdsouthan> @danaklug
<https://github.com/danaklug> @mattodd <https://github.com/mattodd>
@edwintse <https://github.com/edwintse>
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@danaklug @mattodd @edwintse I added the experimental details for all of the compounds made (as well as the synthesis of each of the intermediates) to the Experimental Folder. I also included the links to the ELN pages for each reaction. Those links can be deleted if instead you want me to just send a pdf of the ELN for inclusion in the SI. I also added the metabolic stability data table if any of it can be used in the main body of the paper. I have the EC50 curves for the final products as a pdf and reference to the experimental conditions when needed. Lastly, I have Chemdraw files for all of the synthetic schemes, but I was unsure of how to make a folder in GitHub to place them in. Let me know if you want them and where to place. Thanks. |
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@danaklug and @edwintse I am hoping to devote some time to trying to edit the Series 4 paper. I apologize, but I may not have understood completely the last time we met. Is the latest version of the paper the one on the Google Docs page? Or is there a Word document on one of the repositories? Also, how do the SAR tables on Google docs relate to the paper? Is the table just a summaru for us or will this be part of the SI of the paper? Thank you for any direction. |
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@MedChemProf Great! Yes, the working version is the one on Google Docs. The SAR tables there were done by @danaklug as the initial summary for that section of the paper. We then modified/abbreviated it to what it is in the paper now. We'll need to include all this data in the SI since some compounds won't be included in the main paper, but need to think of a good way to do this (I think they might be a bit unwieldy at the moment). |
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My suggestion @MedChemProf @danaklug @edwintse would be to submit a version of the master sheet with the S4 results in their entirety to Figshare as the SI. The S4 compounds already published (PMID: 32678591, PMID: 32786609) can obviously stay in. This ensures that we would be largely FAIR even if not all the SMILES are in PubChem and/or if not every inactive structure was discussed in the paper
As mentioned before I can attempt to get the top-5 sub uM into PubChem BioAssay directly. Pushing the entire S4 sheet into PubChemBioAssay and/or ChEMBL is more of challenge that we could contemplate but this need not be coupled to the
publication in the first instance (n.b. 1 is the continuation of S4 planned? n.b. 2 see BioITWorld FAIRness presentation by yours truly https://zenodo.org/record/4286545#.X7uzk2hKiUl slides only https://zenodo.org/record/4286507#.X7u1MGhKiUk
…On Mon, Nov 23, 2020 at 11:59 AM Edwin Tse ***@***.***> wrote:
@MedChemProf <https://github.com/MedChemProf> Great! Yes, the working
version is the one on Google Docs. The SAR tables there were done by
@danaklug <https://github.com/danaklug> as the initial summary for that
section of the paper. We then modified/abbreviated it to what it is in the
paper now. We'll need to include all this data in the SI since some
compounds won't be included in the main paper, but need to think of a good
way to do this (I think they might be a bit unwieldy at the moment).
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Given @mattodd s forthcoming move (congrats :) and the imminent output of the S4 paper it might be a good time to cogitate on the next big steps. For example a) will the OSM web stuff and or wet-work be mirrored to Brunswick Square? b) is there a sucession plan for someone to head up the Sydney wet-work c) are we going to draw a line under S4 and move on, since it seems a bit slow going and there are several PfATP4 inhibitors in more advanced stages of development? d) there are still some technical loose ends in our "ways of working" for the future. In particular what about setting up of an institutional figshare repositry (London or Sydney?) that the project data could permenantly persist in?
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