TIME OUT for import_intercell_network

[howtofindme]

Hi
when I run import_intercell_network ,it always throw a time-out. I guess it is a problem of my network.
So, can I imort these network in local? could you give me some hints?

Thanks!
Young

[deeenes]

Hi,

Above we see two different errors from two independent attempts to download the same URL. The first error means the SSL handshake was not completed, your machine was waiting for a packet, sent by our server, that never arrived. The second error happened at a step upstream of the previous one: here your machine asked its DNS server what's the IP address of our server, but the answer has never come. Both errors have one thing in common: a network packet got lost with no trace. It means, either the network your computer is connected to, or a larger network connecting it to the internet is suffering from issues and packets get lost. As you might see, we can not really do anything about this kind of error, but I can give you a few hints:

• Try from another network: from home, from another institute, company, etc.
• Use different DNS servers, possibly one or more well established public servers
• Test your setup with curl -vvv: this error is a basic networking issue, and this way you see all the details of the communication
• Do all your tests a few times, as the errors come randomly
• Try to download some pages from https://omnipathdb.org/, and also from other domains. Good to try for example a server which is close to you, such as a university in your town, and something that is in an international data centre. Use traceroute and whois to find out what is where and the path of network traffic. Observe what kind of errors pop up in each case.
• Try an HTTP client different than libcurl: e.g. open the same URLs in a web browser (in this case look at the Network tab of the Inspector for network errors).

I hope this helps, please let me know if you've more questions.

Best,

Denes

[howtofindme]

Hi,

Above we see two different errors from two independent attempts to download the same URL. The first error means the SSL handshake was not completed, your machine was waiting for a packet, sent by our server, that never arrived. The second error happened at a step upstream of the previous one: here your machine asked its DNS server what's the IP address of our server, but the answer has never come. Both errors have one thing in common: a network packet got lost with no trace. It means, either the network your computer is connected to, or a larger network connecting it to the internet is suffering from issues and packets get lost. As you might see, we can not really do anything about this kind of error, but I can give you a few hints:

• Try from another network: from home, from another institute, company, etc.
• Use different DNS servers, possibly one or more well established public servers
• Test your setup with curl -vvv: this error is a basic networking issue, and this way you see all the details of the communication
• Do all your tests a few times, as the errors come randomly
• Try to download some pages from https://omnipathdb.org/, and also from other domains. Good to try for example a server which is close to you, such as a university in your town, and something that is in an international data centre. Use traceroute and whois to find out what is where and the path of network traffic. Observe what kind of errors pop up in each case.
• Try an HTTP client different than libcurl: e.g. open the same URLs in a web browser (in this case look at the Network tab of the Inspector for network errors).

I hope this helps, please let me know if you've more questions.

Best,

Denes

Dear Denes,
It's a great honor to hear from you. I benefit a lot. I try again by using brower to download your data ,and it works! the link is https://omnipathdb.org/interactions?genesymbols=yes&datasets=ligrecextra,omnipath,pathwayextra&organisms=9606&fields=datasets,sources,references,curation_effort&license=academic

But a new error occurs when I run

###Selecting important features
lig_rec_red <- lig_rec %>% dplyr::ungroup() %>%
dplyr::select(target_genesymbol,source_genesymbol,
is_directed,category_intercell_target)

https://github.com/saezlab/misty_pipelines/blob/0d23e52524375171bd26182892a18fc55b258818/visium/2_run_misty_ppline.R#L30

This means there is no "category_intercell_target" column in your data. I dont known whether the file is correct in your server.

Thanks for your help.
Best wishes,
Young

[deeenes]

Hi Young,

In the OmniPath Interactions database there is no data about intercellular communication roles. Those are stored in our Intercell database: https://omnipathdb.org/queries/intercell. The import_intercell_network in OmnipathR (and also in the Python omnipath module) combines the interactions with the intercellular communication roles to create a cell-cell communication network. As you see in the Visium script that you've linked, lig_rec is the output if this function. If you use the OmniPath Intercell dataset in your work, I recommend to read carefully its description in our paper (also tables EV6 and EV10), and take a look at the quality filtering options. You can also consider this as an alternative.

Overall, I think the better solution to your problem is to fix your original issue with the downloading, and use import_intercell_network.

Best,
Denes

[howtofindme]

Hi Young,

In the OmniPath Interactions database there is no data about intercellular communication roles. Those are stored in our Intercell database: https://omnipathdb.org/queries/intercell. The import_intercell_network in OmnipathR (and also in the Python omnipath module) combines the interactions with the intercellular communication roles to create a cell-cell communication network. As you see in the Visium script that you've linked, lig_rec is the output if this function. If you use the OmniPath Intercell dataset in your work, I recommend to read carefully its description in our paper (also tables EV6 and EV10), and take a look at the quality filtering options. You can also consider this as an alternative.

Overall, I think the better solution to your problem is to fix your original issue with the downloading, and use import_intercell_network.

Best, Denes

Dear Denes,
Really Thanks!

After using another machine, finally I can download your data.

1.But since I can also download your data using browser from archive.omnipathdb.org, I was wondering whether there is a way that I can annotate proteins using import_omnipath_annotations() through the locally downloaded file in my poor-network machine.

2.Following might be some errors, but I am not sure.

2.1 import_intercell_network() works very well.

2.2 but curated_ligand_receptor_interactions() does not work.

2.3 interactions_pathwayextra_mice <- import_pathwayextra_interactions(resources=c("BioGRID","STRING"), organism = 10090) is ok
but interactions_pathwayextra_mice_all <- import_pathwayextra_interactions(resources=get_interaction_resources(), organism = 10090) failed

Best,

Young

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[deeenes]

Hello Young,

Dear Denes, Really Thanks!

After using another machine, finally I can download your data.

1.But since I can also download your data using browser from archive.omnipathdb.org, I was wondering whether there is a way that I can annotate proteins using import_omnipath_annotations() through the locally downloaded file in my poor-network machine.

Technically it's possible, but then you have to write quite some code that is already written in the OmnipathR package. It would be time consuming and error prone. All this because of a poor network. If I had no other choice than dealing with that network, I would start with recording some curl debug logs to find out what's going on, why the network transactions fail. Otherwise far the easiest option for you is to get access to a good network.

Also, OmnipathR stores the downloaded data in its local cache, so once you downloaded everything in your script, no network transactions are necessary (there might be a few exceptions).

2.Following might be some errors, but I am not sure.

2.1 import_intercell_network() works very well.

Yes, this worked well, but the warning message is still worrying: it means that some unexpected type of value was encountered when processing the data, and this shouldn't happen. Maybe it's also a networking error, and one of the responses was not fully transmitted. You can wipe the cache directory and try again.

library(OmnipathR)
omnipath_cache_wipe()

You can also inspect the resulted data frame if all columns and their types look alright. To do this, simply print the data frame to the terminal.

2.2 but curated_ligand_receptor_interactions() does not work.

This is again a download error, and I'm sure this download has been performed successfully in many of your earlier calls. It's likely just by accident, it makes sense to try again a few times. This file (https://omnipathdb.org/resources) is downloaded by jsonlite::fromJSON, which uses curl as its HTTP backend, so you can investigate by curl debug logs.

2.3 interactions_pathwayextra_mice <- import_pathwayextra_interactions(resources=c("BioGRID","STRING"), organism = 10090) is ok

It's not okay, it returned 0 interactions :)
I don't think it makes sense to pass get_interaction_resources() to import_pathwayextra_interactions: the former returns all interaction resources (including TF, miRNA and small molecule interactions), while pathwayextra itself is already a set of resources. If you don't want some of those, use the exclude parameter, if you only want some of them, list them in the resources parameter.

but interactions_pathwayextra_mice_all <- import_pathwayextra_interactions(resources=get_interaction_resources(), organism = 10090) failed

It hasn't failed, it only sent a warning
But indeed, STRING is not redistributed in OmniPath, and while we have some interactions annotated from BioGRID, I wouldn't recommend accessing specifically BioGRID by OmniPath: most of its content is not included in our data, as it consists of undirected interactions from large screens.

Best,

Young

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[1] /usr/local/lib/R/site-library [2] /usr/lib/R/site-library [3] /usr/lib/R/library

Thanks for the session info, it's good to see that packages are up to date and you're using Linux.
Btw, instead of inserting pictures, you can copy-paste the text in code blocks by using triple backticks.

Best,
Denes

[howtofindme]

Hello Young,

Dear Denes, Really Thanks!
After using another machine, finally I can download your data.
1.But since I can also download your data using browser from archive.omnipathdb.org, I was wondering whether there is a way that I can annotate proteins using import_omnipath_annotations() through the locally downloaded file in my poor-network machine.

Technically it's possible, but then you have to write quite some code that is already written in the OmnipathR package. It would be time consuming and error prone. All this because of a poor network. If I had no other choice than dealing with that network, I would start with recording some curl debug logs to find out what's going on, why the network transactions fail. Otherwise far the easiest option for you is to get access to a good network.

Also, OmnipathR stores the downloaded data in its local cache, so once you downloaded everything in your script, no network transactions are necessary (there might be a few exceptions).

2.Following might be some errors, but I am not sure.
2.1 import_intercell_network() works very well.

Yes, this worked well, but the warning message is still worrying: it means that some unexpected type of value was encountered when processing the data, and this shouldn't happen. Maybe it's also a networking error, and one of the responses was not fully transmitted. You can wipe the cache directory and try again.

library(OmnipathR)
omnipath_cache_wipe()

You can also inspect the resulted data frame if all columns and their types look alright. To do this, simply print the data frame to the terminal.

2.2 but curated_ligand_receptor_interactions() does not work.

This is again a download error, and I'm sure this download has been performed successfully in many of your earlier calls. It's likely just by accident, it makes sense to try again a few times. This file (https://omnipathdb.org/resources) is downloaded by jsonlite::fromJSON, which uses curl as its HTTP backend, so you can investigate by curl debug logs.

2.3 interactions_pathwayextra_mice <- import_pathwayextra_interactions(resources=c("BioGRID","STRING"), organism = 10090) is ok

It's not okay, it returned 0 interactions :) I don't think it makes sense to pass get_interaction_resources() to import_pathwayextra_interactions: the former returns all interaction resources (including TF, miRNA and small molecule interactions), while pathwayextra itself is already a set of resources. If you don't want some of those, use the exclude parameter, if you only want some of them, list them in the resources parameter.

but interactions_pathwayextra_mice_all <- import_pathwayextra_interactions(resources=get_interaction_resources(), organism = 10090) failed

It hasn't failed, it only sent a warning But indeed, STRING is not redistributed in OmniPath, and while we have some interactions annotated from BioGRID, I wouldn't recommend accessing specifically BioGRID by OmniPath: most of its content is not included in our data, as it consists of undirected interactions from large screens.

Best,
Young
sessioninfo::session_info() ─ Session info ────────────────────────────────────────────────────────────────────────────────────────────────── setting value version R version 4.3.1 (2023-06-16) os Ubuntu 20.04.6 LTS system x86_64, linux-gnu ui RStudio language (EN) collate en_US.UTF-8 ctype en_US.UTF-8 tz Asia/Shanghai date 2023-10-11 rstudio 2023.06.2+561 Mountain Hydrangea (server) pandoc 3.1.1 @ /usr/lib/rstudio-server/bin/quarto/bin/tools/ (via rmarkdown)
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[1] /usr/local/lib/R/site-library [2] /usr/lib/R/site-library [3] /usr/lib/R/library

Thanks for the session info, it's good to see that packages are up to date and you're using Linux. Btw, instead of inserting pictures, you can copy-paste the text in code blocks by using triple backticks.

Best, Denes

Dear Denes,

Thanks for your patient and comprehensive answer. Your suggestion of using "triple backticks" was particularly helpful to me.

Thank you once again.

Best regards,
Young