Editing Session: Friday 2/7

[danaklug]

Hi everyone, next editing session will be Friday, July 2 at 6:00am Boston/11:00am London/8:00pm Sydney.

Discussion to be focused on the conclusion, and determining which compounds should be highlighted as the most "balanced" in terms of potency and ADME properties.

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Dana Klug is inviting you to a scheduled Zoom meeting.

Topic: OSM Series 4 Paper Editing
Time: This is a recurring meeting Meet anytime

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Meeting ID: 940 3322 8077
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[MedChemProf]

@danaklug @edwintse @mattodd I was wondering if someone could refresh my memory. Once the manuscript review by the authors is complete and the paper is finalized / reformatted for submission, were we just going to exchange the MMV numbers for OSM numbers? Or were we going to re-number the molecules numerically (1, 2, 3, ...) with a matrix relating the compounds back to their MMV/OSM numbers in the supplemental? My memory was telling me the latter scenario, but I wanted to confirm prior to starting the process and investing too much time if I was wrong. Thanks.

[edwintse]

@MedChemProf I believe we decided on going with OSM numbers. I've been having a look at doing up the SAR figures for publication to make things look a bit neater and have already converted them to OSM numbers (it already looks much better than having MMV numbers) but if you're free to change over the MMV numbers to OSM in the main text then go for it!

[MedChemProf]

@edwintse I can do that. I will give the authors into next week to make additional comments before starting to switch out the numbers in the text. Also, you probably already know this, but if you need the ChemDraw file for any of the current figures, they are now contained in the newly created folder here: https://github.com/OpenSourceMalaria/OSMSeries4Paper1/tree/master/Active%20Paper%20Figs%20Schemes

[MedChemProf]

@edwintse @danaklug @mattodd I made all of the MMV# to OSM# changes to the body of the manuscript. While doing that, I noticed a couple of incorrectly numbered compounds in Figure 2. I know you mentioned you were editing the figures, but I wanted to make sure the numbers the draft match between the test and figures, so I edited all of the figures to include the OSM #'s. I realize that you may replace some of the figures, but I did not want to lose track of the correlation between the test and figures. I also added another compound into Figure 2 (OSM-X-007) with a chloro and the 8-position.

One item that we may have to revisit is the activities of the different isomers of the compounds substituted with a methoxy group at the benzylic position (OSM-S-272). After looking at the raw data in the Master Sheet, I was not confident of some of the discussion of activity versus chirality. I edited the structures to remove the assignment of chirality in the inherited compound. If there is another source of data, please let me know. Thanks.

[MedChemProf]

@edwintse @danaklug @mattodd I just uploaded an excel file into the 'Active Paper Figs Schemes' folder that contains a list of compounds currently in the manuscript sorted by their OSM ID and correlated with their MMV ID and SMILES. I though this might me useful if we have to renumber the compounds following reviewer comments.

[cdsouthan]

@MedChemProf crucial good job but please post the direct link. What is the state of synchronisation between @edwintse @OSMSeries4Paper1/SI Files/OSM Master Sheet Extract.xlsx and the list mentioned above? Also, given the multiple activity values how were the pfal EC50s in the draft paper selected? For the record its good 2 c OSM numbers as primary IDs, otherwise it looked like an MMV paper.....

[MedChemProf]

@cdsouthan Link here. The OSMSeries4Paper1 manuscript reports data from the Master Sheet. The list I created is just for accounting purposes at the moment and also to make renumbering to 1, 2, 3, ... easier in the future if so needed.

[cdsouthan]

Ta, @MedChemProf I was able to map 36 of the 84 SMILES to PubChem CIDs, mostly ChEMBL entries from back in the day. I am going to try for the 10 front-runners by potency a) get submitted if missing and b) get BioAssay entries, Wish me luck.....

[MedChemProf]

@mattodd @edwintse @danaklug Might it be a good time to schedule another manuscript meeting to discuss next steps? Thank you.

[cdsouthan]

Two down :) only ~ 45 to go, :( but getting used to the system again for moderate scale up

[MedChemProf]

@danaklug I am unfamiliar with how best to create and number the citations in the manuscript in google docs. I went through the citations created a list of references formatted for submission to JMedChem. I do not know if this will be helpful or not for how you are approaching the numbering. Please keep me posted on your approach since I would like to learn. Thanks.

[MedChemProf]

@danaklug @mattodd @edwintse I found an Add-On tool for Google Docs called SciWheel for adding and formatting of references. It worked pretty well and was easy to use once I uploaded all of the references into the tool. I went ahead and completed the references for the manuscript. I edited out the [ ] bracketed DOI's. I have a saved copy prior to the change if needed. I have one issue that we can probably change later in that we have 1 footnote that also uses a numeral. I just highlighted the footnote number for the time being.

[cdsouthan]

Have we decided to submit to ACS Central Science as for the previous effort? (the Editor may even remember us :)

N.b. just saw this in Twitter

[MedChemProf]

@edwintse @danaklug @mattodd I just wanted to suggest that we hold a brief meeting to touch base on the manuscript. I believe some action items may be ongoing, but getting an update will help keep everyone on the same page. Thanks, Chase

[mattodd]

Hi @MedChemProf agreed, sorry for the slow response. Next week sometime? Could do 1pm UK most days. Or 4pm Mon, Wed, Thur.

Actions that I know are outstanding

1. Ed to check Pfizer NMR data that came in
2. Ed talking to Alice about data still needed for the SI
3. Mat checking on authorship vs acknowledgement for Sue C
4. Sorting out Labtrove dumps so that we can archive somewhere permanent (in touch with Jeremy Frey about this, and there's movement forward).
   I think that's all the actions so far.
   We have a residual issue re publication venue - UCL can't guarantee to cover APCs for hybrid journals, so we will either need to secure agreement from a funder that the APC for e.g. J Med Chem would be covered, or we publish in a genuine open access journal (gold, platinum) - i.e. one where all the papers are open access.

[MedChemProf]

@mattodd @edwintse @danaklug I am available at 8am (East Coast USA) / 1pm (UK) any day next week (Sep 20 - 24). Please let me know you preferences. Thanks!

[alintheopen]

Hi folks, I think that's 10pm AEST - I can do Tue/Wed/Thur with preference for Wed/Thurs

[MedChemProf]

@alintheopen @mattodd @edwintse @danaklug Thank you all. I propose then we meet on Wednesday, September 22nd 10:00 pm Sydney, 1:00 pm London, 8:00 am Boston. Below is the Zoom meeting information again:

Join Zoom Meeting
https://ucl.zoom.us/j/94033228077

Meeting ID: 940 3322 8077

[MedChemProf]

@cdsouthan I just uploaded a spreadsheet of the information that you requested. It can be found here.
The first column is a lookup of the OSM number to see if it is in the manuscript. Any row with an OSM number in the first column is in the paper. The remaining columns are identifiers (OSM, MMV numbers, SMILES, InChi, InChi Key) and any data associated with the compound. Please let me know if you have any questions.

[MedChemProf]

@mattodd @danaklug @edwintse Dear All, I was hoping we might revisit the Series 4 manuscript. At the moment things have seemed to stall and I would like to discuss the possibility of a path for restarting and continuing forward progress. Thank you.

[MedChemProf]

From the number of posts on Twitter regarding the OSM's recent publication and also all of the work going on in the open-source antibiotics, it is clear that all of you very talented scientists are extremely busy and productive! Might I, however, take up a little bit of your time in the near future? I was hoping to revisit the Series 4 manuscript. Thank you.

[cdsouthan]

Updates 17 Dec

From the file of 83 compounds Chase sent me (thanks :) 36 were already in PubChem BioAssay via ChEMBL and a few from me (OSM-W-009 and 010 were duplicates so best to back-purge one of them and resolve an associated data to avoid future noise)

The rest I have submitted SIDs for
https://www.ncbi.nlm.nih.gov/pcsubstance?term=%22Chris%20Southan%22%5BSourceName%5D&cmd=DetailsSearch

So we have an (almost) complete mapping set as "New mapping" in the attached sheet [Chase_compounds for paper Dec.xlsx]

Maybe Chase could do the sorting to line up the ducks for the table in the paper and add the activity values

We have two"reticents". While I dont think it is personal PubChem does not like those boranes in https://pubchem.ncbi.nlm.nih.gov/#query=OSM-S-418. I can ask them but is there an alternative SMILES configuration that might make in more likely to pass the CID rules? Not sure what happen with 411, I will have to resubmit

Note that if the journal allows we could make the CID links live in the published version .

Just now I don't have the perspicacity to grapple with a PubChem BioAssay submission but there are other options.

The simplest is if when we get the eventual PMID I can just add that pointer to all the SIDs so anyone could get back to activity via the paper (this would be have interesting PubChem <> PubMed linking consequences.

Another is to eventually submit to ChEMBL (again). However, since Anna Gaulton is leaving we will need another contact to help us. If this goes well there is an argument for just depositing the whole OSM data sheet (just take the lowest IC50s)

I can write a short section on how this was done and add some FAIR-ness context - if there is room left in the paper

If LabTrove does not get fixed do we have a contingency plan? (e.g. old fashioned synthesis descriptions)

Cheers, Chris

Chase_compounds for paper Dec.xlsx

[mattodd]

Hi @cdsouthan - great, thanks. So, just extracting the action points:

• When you say "the sorting to line up the ducks for the table in the paper and add the activity values" what's needed for the paper submission?
• Would you mind asking Pubchem to see if they can sort 418 and 411? They must have compounds with boranes already (@edwintse ?)
• For all compounds on Pubchem we eventually just add the link to the paper, right? So we do that later, right?
• Yes, a few lines of text for the SI describing what you did would be v useful, thank you. If you write below, we can paste in.
• We already have synthesis descriptions, the Labtrove thing is for all the actual experiments. I think we can solve it.