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Add cell-cell communication chapter #140

Merged
merged 21 commits into from
Jan 24, 2023
Merged

Add cell-cell communication chapter #140

merged 21 commits into from
Jan 24, 2023

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dbdimitrov
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Hi @AnnaChristina @Zethson,

As discussed, this is my draft for the CCC chapter.

In short, I give a general background on CCC, run CellPhoneDB, LIANA and NicheNet; summarize some of the assumptions and limitations of CCC in single-cell transcriptomics, and give an outlook with a few questions as a quiz.

I included a couple of example figures, I guess they don't exactly fit the style of the book. Nevertheless, the ideas are there, even though my artistic skills are not :)

Several things to note:

  • Checks took a while (pre-commit specifically?, we might want to check why)
  • The Wang data is paired we might want to do a paired test, but honestly a jump to limma for NicheNet is going to push it too much imho.
  • I link to other chapters in several places already, because some background knowledge is need to understand the methods.

If we're looking for a second opinion, we could ask Erick Armingol, Hratch Baghdassarian, or Robin Browaeys.
Once I get some feedback, I'm happy to go over the chapter again to address any comments and fix potential typos, etc.

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@github-actions github-actions bot added the enhancement New feature or request label Jan 10, 2023
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Zethson commented Jan 10, 2023

Awesome, this is really cool! I'll start with some comments in a moment :)

Checks took a while (pre-commit specifically?, we might want to check why)

Surprises me. They're usually somewhat instant for me. I'll keep an eye on it.

If we're looking for a second opinion, we could ask Erick Armingol, Hratch Baghdassarian, or Robin Browaeys.

Yeah, that would be great. I fully trust you to pick someone that is competent but also enjoys reviewing such work.

@Zethson Zethson changed the title Feature/ccc Add cell-cell communication chapter Jan 10, 2023
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Zethson commented on 2023-01-10T21:32:25Z
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This section is usually always called "motivation" in our book. Please rename it although "background" is of course a perfectly valid name.


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Zethson commented on 2023-01-10T21:32:26Z
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transcritpomics

-> transcriptomics

commonly referred as ligand-receptor

-> commonly referred to as ligand-receptor

plagued by the lack of ground truth

-> plagued by a lack of ground truth

You can mention at the end why we're now showing which methods then.


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Zethson commented on 2023-01-10T21:32:28Z
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Please talk to Anna about the figure. She will redraw it.


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Zethson commented on 2023-01-10T21:32:29Z
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Rename to "Environment setup", please.


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Zethson commented on 2023-01-10T21:32:29Z
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Citation isn't done :)


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Zethson commented on 2023-01-10T21:32:30Z
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TODO: replace with pertpy dataloader soon. Likely next week or so.


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Zethson commented on 2023-01-10T21:32:31Z
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Line #1.    # Check cell types

Rather write some text above such as:

"We are examining the cell types for x y z reason".


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Zethson commented on 2023-01-10T21:32:32Z
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Line #1.    # show UMAP as a refresher

Rather write some text above as in: "Let's look at xyz for abc reason first"


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Zethson commented on 2023-01-10T21:32:33Z
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Explain these choices.


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Zethson commented on 2023-01-10T21:32:34Z
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Explain these choices


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Zethson commented on 2023-01-10T21:32:35Z
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Can you kill some of these warnings upstream? :)


dbdimitrov commented on 2023-01-11T14:40:21Z
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Yep, updated liana to get rid of those :)

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Zethson commented on 2023-01-10T21:32:36Z
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Visual exploration

or something else. At least without the typos :)


dbdimitrov commented on 2023-01-11T09:08:16Z
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hahahaha that typo is a work of art

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Zethson commented on 2023-01-10T21:32:37Z
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If you're not going to reuse the plot you don't need to assign it to a variable.


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Zethson commented on 2023-01-10T21:32:38Z
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specicity

specificity


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Zethson commented on 2023-01-10T21:32:39Z
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distrubtion

distribution


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Zethson commented on 2023-01-10T21:32:40Z
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See above.


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Zethson commented on 2023-01-10T21:32:41Z
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I like this section. Well done.


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grst commented on 2023-01-12T10:27:23Z
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Personally, I think comparisons between conditions are quite important and I'd even argue it's what most of the people want most of the time.

Therefore, I'd at least love to see that outlook section expanded a bit beyond a reference to the papers (e.g. summarizing what the methods do and linking to their tutorials).

Also, as far as I understood, NicheNet, as applied in this tutorial is also based on comparison between conditions, so maybe worth referencing this here.


dbdimitrov commented on 2023-01-19T19:25:03Z
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Yep. Great point, I will adapt the NicheNet part to reflect that.

dbdimitrov commented on 2023-01-22T14:31:33Z
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I also extended the outlook a bit in this direction, but honestly I wouldn't personally apply most methods. Many of them focus on interaction numbers between cell types (which I don't think is super meaningful) and few approaches were actually benchmarked.

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grst commented on 2023-01-12T10:27:24Z
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  1. Something seems wrong with the formatting in

nt the subunit with minimum expression, while *complex corresponds to the actual complex, with subunits being separated by .

  1. as each method infers relies on
  2. and the other reflects how the specificity of
  3. to a pair of cell identities

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grst commented on 2023-01-12T10:27:25Z
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hypothesis-free systems-level hypotheses

sounds a bit weird


dbdimitrov commented on 2023-01-20T14:21:42Z
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"to generate systems-level insights in a hypothesis-free manner" should be clearer :)

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grst commented on 2023-01-12T10:27:26Z
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NicheNet first employs a network algorithm, known as Personalized PageRank, to estimate the probability of a random walk from a ligand to terminate at a given regulator, or it estimates the signalling probability of a given ligand modulating a particular regulator.

I don't get how the "estimates the signalling probability of a given ligand modulating a particular regulator" connects to the random walk. Is this an alternative approach? Then how does it estimate the probability?


dbdimitrov commented on 2023-01-20T15:43:25Z
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yep, extended it a bit :)

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grst commented on 2023-01-12T10:27:27Z
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  • Is there something wrong with the enumeration, or is this ReviewNB?
  • Should Outlook become a H2? I almost missed it...

---

Comparison between conditions: is CellphoneDB v3 one of them?


dbdimitrov commented on 2023-01-22T10:00:47Z
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I believe the v3 version of CPDB asks the user for DE genes and returns interactions which contain those. However, even if these are DEGs between conditions, I'm not sure if it is an actual method to do comparison between conditions.

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grst commented Jan 12, 2023

Really nice write-up, @dbdimitrov!

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Yep. Great point, I will adapt the NicheNet part to reflect that.


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dbdimitrov commented on 2023-01-19T19:25:18Z
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Prior to that should add technical considerations, expression proportions, complexes, stable cell types, etc.


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dbdimitrov commented on 2023-01-19T19:25:19Z
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Robin: Other way around would be clearer, e.g. multiple senders, only one receiver.


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"to generate systems-level insights in a hypothesis-free manner" should be clearer :)


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yep, extended it a bit :)


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OK. Fair point, I can load e.g. dplyr and tdyr for my part alone, but then NicheNet includes most of tidyverse as imports, and Seurat (which itself imports half of CRAN and 90% of BioConductor).


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I believe the v3 version of CPDB asks the user for DE genes and returns interactions which contain those. However, even if these are DEGs between conditions, I'm not sure if it is an actual method to do comparison between conditions.


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Updated these with Anna's figures :)


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I also extended the outlook a bit in this direction, but honestly I wouldn't personally apply most methods. Many of them focus on interaction numbers between cell types (which I don't think is super meaningful) and few approaches were actually benchmarked.


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Changed this and reduces some of the dependencies in the env


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Excellent work! Thank you very much. I'll now integrate it into the book

@Zethson Zethson merged commit ac4ea25 into development Jan 24, 2023
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grst commented Jan 24, 2023

@dbdimitrov, I'd definitely like to hear more about your thoughts on Cell2cell comparisons between conditions, but this is not the right place to discuss it! Maybe I'll open an issue in Lianapy?

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@grst yes, please do so :) We have been working on bridging the two (liana x Tensor) a lot lately, so I plan to add a tutorial soon. We're also working on a bit more in-depth tutorials, and I hope these will be available in the next month or so.

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