Chromatograms always get written to disk, but you are probably asking how much memory does the computer need to have to keep everything in memory that needs to be in memory.
The amount of RAM that Skyline needs is usually determined by the number of rows that you see in the Transition Results report in the Document Grid. That is, the number of transitions times the number of replicates is a good indicator of how much RAM Skyline is going to need. Skyline needs about 200 bytes per thing that represents a row in the Transition Results report.

So, if your document had 1 million transitions and 100 replicates, then Skyline would probably be able to get by with using 20GB RAM.

The length of the chromatograms does not usually matter because the chromatograms only get loaded from the .skyd file when the graphs are being displayed to you and during peak detection. The .skyd file can be much larger than the amount of RAM in the computer.
-- Nick

so I'm having to break up transition lists into 1000 line sets in order to avoid having the reading of a single result file stalling out on a computer with 32GB of RAM. The CPU is not significantly stressed but the RAM is. It's not every transition list but enough that it's a problem. Maybe I need to ask the question another way, are there sets of transitions that we know lead to result importations that run out of RAM?

Can you send us your Skyline document and your raw files?
In Skyline you can use the menu item:
File > Share
to create a .zip file containing your Skyline document and supporting files.

You can upload the raw files that you were hoping to import and that zip file here:
https://skyline.ms/files.url

Extracting chromatograms is not supposed to require much RAM. Skyline is supposed to start writing the partially extracted chromatograms to disk before they consume any significant amount of memory. Unfortunately, every once in a while a bug creeps in which causes Skyline to not do that, or, for some other reason, to be using a lot more memory than it's supposed to.

After we see your Skyline document and your raw files we will be able to figure out what is going wrong.
-- Nick

Thank you for uploading that transition list.
I see that your transition list has 5000 transitions all under the same precursor.
It's likely that the performance problems that you are seeing are not related to memory, but there might instead be some algorithms that Skyline uses which do not scale well with the number of transitions that a single precursor has.

Is there a reason that all of the transitions are under the same precursor? When transitions are under the same precursor in Skyline, Skyline expects that they will have the same peak integration boundaries.
-- Nick

Yes,

ultimately the reason for the comprehensive transition profile per precursor is that I'm not just using the msms spectra to assign peptides but to distinguish regioisomers. My transition lists are exhaustive but they are based on things that I see in these data and to address the various issues coherently I wanted the transition lists to be comprehensive.

I know my application is off axis and you are in no way obligated to address it.

if there is away to make that algorithmic punishing of high transition counts optional, it would be incredible.

Can you send us a Skyline document with even more transitions per precursor? We will try to fix Skyline so it takes a more reasonable time.
It's always helpful to see unusual documents like this because the things that are making Skyline slow are often straightforward for us to fix.

In Skyline you can use the menu item:
File > Share
to create a .zip file containing your Skyline document.

You don't need to import results into that document since it will probably end up taking too long. But, if you could send us one of the raw files you were planning to import then that would be helpful. You don't need to send us the raw data again if it's the same file you already sent us.

For raw data that is in a folder, it's usually easier for you to package it in a .zip file before uploading it.

Files which are less than 50MB can be attached to these support requests. You can always upload larger files here:
https://skyline.ms/files.url
-- Nick

This has 20,000.

I was hoping you would send me a Skyline document instead of just a transition list because I was not sure what settings you have on the "Full Scan" tab of "Settings > Transition Settings".

Could you send me a Skyline document? You can use the "File > Share" menu item to create a .zip file.
-- Nick

Sorry! Here's the skyline doc, and yes, the data is not centroided.