Editing Session: Monday 25/1/2021

[danaklug]

Following Chase's hard work on the Series 4 manuscript, Mat and I have discussed having an editing session over Zoom on Monday 25/1 to discuss the manuscript thus far and resolve any outstanding issues.

Scheduling will be challenging since we have contributors in the US, UK, and Australia. The following time slots seem most reasonable to me although still a bit early/late for some. Hopefully one of them will work for enough people that the session will be productive!

A 6am Boston/11am London/10pm Sydney B 2pm Boston/7pm London/6am Sydney (Tues 26/1) C 3pm Boston/8pm London/7am Sydney (Tues 26/1) D 4pm Boston/9pm London/8am Sydney (Tues 26/1)

Please comment below with availability @MedChemProf @mattodd @edwintse @cdsouthan @alintheopen @drc007 et al!

[MedChemProf]

@danaklug I can make meetings A and D. If B was the selected time, I could attend for about 30 minutes before having to leave for another meeting (which also eliminates meeting C for me.) Thank you for organizing.

[mattodd]

Thanks @danaklug. Like @MedChemProf I can make A or D, with a preference for A if it's a tie break.

Additionally pinging @holeung

Long overdue thanks to anyone who made edits over the festive season, particularly @MedChemProf

For readability purposes, and should people have time, it'd help if the citations could be moved from the main text to the ref list at the end. In-text citation markers can be based on DOI or author-year.

Also, could I urge anyone with original figures/schemes to share those on this repository (in the shared file system under "code"). If this is tricky, we can discuss, but it helps if we have a shared store of files for the paper. This is particularly important for the SI section, obviously.

And I know I've asked this before, but do we have a link to the current file containing synthetic chemical methods and characterization data? Really don't want to be in the position of having overlooked the need for a HRMS or something.

[edwintse]

I'd also prefer A or D (leaning towards A in a tie break as well). Thanks @danaklug!

[maratsydney]

I am also most comfortable with A or D, with no real preference.

[drc007]

No preference

Chris

On 19 Jan 2021, at 17:25, Dana Klug notifications@github.com wrote:

Following Chase's hard work on the Series 4 manuscript, Mat and I have discussed having an editing session over Zoom on Monday 25/1 to discuss the manuscript thus far and resolve any outstanding issues.

Scheduling will be challenging since we have contributors in the US, UK, and Australia. The following time slots seem most reasonable to me although still a bit early/late for some. Hopefully one of them will work for enough people that the session will be productive!

A 6am Boston/11am London/10pm Sydney B 2pm Boston/7pm London/6am Sydney (Tues 26/1) C 3pm Boston/8pm London/7am Sydney (Tues 26/1) D 4pm Boston/9pm London/8am Sydney (Tues 26/1)

Please comment below with availability @MedChemProf https://github.com/MedChemProf @mattodd https://github.com/mattodd @edwintse https://github.com/edwintse @cdsouthan https://github.com/cdsouthan @alintheopen https://github.com/alintheopen @drc007 https://github.com/drc007 et al!

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[danaklug]

Thanks everyone, looks like A is the winner. Zoom details below:

Dana Klug is inviting you to a scheduled Zoom meeting. Join Zoom Meeting https://ucl.zoom.us/j/96918748955 Meeting ID: 969 1874 8955 One tap mobile +13126266799,,96918748955# US (Chicago) +19292056099,,96918748955# US (New York) Dial by your location +1 312 626 6799 US (Chicago) +1 929 205 6099 US (New York) +1 301 715 8592 US (Washington D.C) +1 346 248 7799 US (Houston) +1 669 900 6833 US (San Jose) +1 253 215 8782 US (Tacoma) Meeting ID: 969 1874 8955 Find your local number: https://ucl.zoom.us/u/adBDOt9yGX

[cdsouthan]

Look forward but can only make first 30 mins, Cheers

[jonjoncardoso]

Hi! I might also attend tomorrow, it will be nice to get to see everyone

[MFernflower]

I will not be able to attend

[mattodd]

Thanks for today's session @jonjoncardoso @drc007 @cdsouthan @danaklug @MedChemProf @edwintse @maratsydney and Peter Rutledge (what's his handle again?). Very useful. Will post actions etc ASAP. Dana would you be able to set up an identical meeting for 2 weeks' time? Everyone: no pressure to come, but great if you're able. Managed to grab a quick screenshot before everyone left. Good to see you all...

[drc007]

@mattodd @danaklug What do you think of something like this?

[danaklug]

@drc007 Yes, I think this type of plot is better although the Y-axis looks a little wonky to me (is it log scale or no?) and maybe we can tweak the colors to the red-amber-green that we've been using throughout the paper?

FYI all - Zoom details for the next editing session are posted at #32.

[mattodd]

Yes, I like it @drc007 and agree with the colour coding @danaklug mentions. Scale looks like a clever compromise of compression and spacing, but the choice of axis markers makes it look odd. Maybe just alter the numbers chosen for the marks? So @edwintse the full set goes in the SI. We could always include in the above figure one representative structure of each class? @edwintse could you pass this by Kiaran Kirk and Adele Lehane when we have a diagram and an SI table ready? Clearly we're also going to want his inputs on the text in the paper, but this is just to ensure that he's happy with the representation.

[drc007]

@danaklug @mattodd Thanks for the input, the colours are just the default I can change them easily. It is just a simple log scale (we have to display 4 orders of magnitude) I'll make that more explicit on the axis. Do we want to include more data points?

[danaklug]

@drc007 Can we see what it looks like including all compounds for which we have data for both assays? Maybe in that case the circles would have to be a bit smaller...

[drc007]

Sure, I just need the data

On 26 Jan 2021, at 17:37, Dana Klug notifications@github.com wrote:

@drc007 https://github.com/drc007 Can we see what it looks like including all compounds for which we have data for both assays? Maybe in that case the circles would have to be a bit smaller...

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[danaklug]

@drc007 I've just sent by email. Thank you!!

[drc007]

@danaklug @mattodd This all the data, to avoid points overlapping I used "bee swarm" spreading points with the same y value along the X-axis. This means we can avoid the log scale. Easy to modify the display now I have all the data. There are a couple of outliers but the conclusion seems pretty robust. The outliers are highlighted in the image below, might be worth rechecking results?

[danaklug]

Yep, I think this looks great and makes the point very nicely!

[edwintse]

@MedChemProf regarding the 3 non-OSM compounds in the paper that had MMV numbers, the structures are (thanks to @PaulWillisMMV for clarifying): cdx file

[MedChemProf]

@danaklug @mattodd I updated Scheme 1 and associated text to address comments. I also moved all of the full reference information to the back of the paper and only left the DOI's in brackets in the text to simplify proofing. I also corrected values and structures in Table 1. I only included data and structures if the information was on the Master Data Sheet. Finally, I added the structures into Figure 10 which were missing (Thanks @edwintse). Please let me know if I missed any of my editing tasks.

[PaulWillisMMV]

Please can we remove the MMV numbers for these 3 PfATP4 inhibitors for the paper. It’s an internal MMV numbering system and is not needed for the publication

Thanks

Paul

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From: cdsouthan notifications@github.com Sent: Thursday, January 28, 2021 4:44:41 PM To: OpenSourceMalaria/OSMSeries4Paper1 OSMSeries4Paper1@noreply.github.com Cc: Paul Willis willisp@mmv.org; Mention mention@noreply.github.com Subject: Re: [OpenSourceMalaria/OSMSeries4Paper1] Editing Session: Monday 25/1/2021 (#31)

@MedChemProfhttps://github.com/MedChemProf @edwintsehttps://github.com/edwintse As best as I can determine

MMV00073 = KAE609 = Cipargamin = https://www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=9721 = PubChem CID 44469321 = CKLPLPZSUQEDRT-WPCRTTGESA-N = C[C@H]1CC2=C([C@]3(N1)C4=C(C=CC(=C4)Cl)NC3=O)NC5=CC(=C(C=C25)F)Cl

MMV390482 = SJ733 = https://www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?ligandId=9723 = PubChem CID MMV397264 = PA21A02

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[cdsouthan]

Apols closed by mistake @danaklug please open again

[cdsouthan]

@MedChemProf We are getting some cross-over duplication with Github posts and Googledoc comments. Not the end of the world for sure but any plan to keep separate?

On Thu, Jan 28, 2021 at 4:14 PM Chase Smith notifications@github.com wrote:

@danaklug https://github.com/danaklug @mattodd https://github.com/mattodd I updated Scheme 1 and associated text to address comments. I also moved all of the full reference information to the back of the paper and only left the DOI's in brackets in the text to simplify proofing. I also corrected values and structures in Table 1. I only included data and structures if the information was on the Master Data Sheet. Finally, I added the structures into Figure 10 which were missing (Thanks @edwintse https://github.com/edwintse). Please let me know if I missed any of my editing tasks.

— You are receiving this because you were mentioned. Reply to this email directly, view it on GitHub https://github.com/OpenSourceMalaria/OSMSeries4Paper1/issues/31#issuecomment-769153299, or unsubscribe https://github.com/notifications/unsubscribe-auth/AA4KXE4MKLFF5YCJNUM5FLLS4F5NVANCNFSM4WJDNSVQ .

[cdsouthan]

@MedChemProf @edwintse @mattodd As best as I can determine (revised 30 Jan)

MMV00073 = KAE609 = Cipargamin = https://www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=9721 = PubChem CID 44469321 = CKLPLPZSUQEDRT-WPCRTTGESA-N = C[C@H]1CC2=C([C@]3(N1)C4=C(C=CC(=C4)Cl)NC3=O)NC5=CC(=C(C=C25)F)Cl

MMV390482 = SJ733 = https://www.guidetomalariapharmacology.org/GRAC/LigandDisplayForward?ligandId=9723 = PubChem CID 89508529 = VKCPFWKTFZAOTO-LEWJYISDSA-N = C1=CC=C2C(=C1)C@@HC(=O)NC4=CC(=C(C=C4)F)C#N

MMV397264 = ? OSRA from the image above https://cactus.nci.nih.gov/cgi-bin/osra/index.cgi gave CC(C)C2=NC1=C(C=CC=C1)[N]2CC(=O)NC3=C(C(=N[N]3C)C)C4=CC=CC=C4

PA21A092 by public name-to-struc is a Kirk compound from https://pubmed.ncbi.nlm.nih.gov/25422853/ and annotated in the Guide to Malarial Pharmacology

N-(4-(4-Chloro-2-Fluorophenyl)-1,3-Dimethyl-1H-Pyrazol-5-Yl)-2-(2-Isopropyl-1H-Benzo[D]Imidazol-1-Yl)Acetamide; PA92; SCHEMBL16402321; GTPL10415; PA21A092; ... https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=10415 CID: 85470655 MF: C23H23ClFN5O MW: 439.9g/mol, InChIKey: AXHVMTZWSKDPRR-UHFFFAOYSA-N

Minimum parsimony therefore indicates the image above associated with MMV397264 is not PA21A092

(Isn't ID cross-mapping just the most fun ... :)

General comment: it is prudent of PW to request the expunging of MMV numbers that, in the wild, would just add to the synonym soup. Giving them an OSM ID and adding to the master sheet is a moot point since the project has not tested them. Could we get them ordered and assayed in // with our best leads?

[mattodd]

Looks like nothing in this Issue remains active, so I'm closing.