First, uncheck the first checkbox in that grid.
Then, press Ctrl + Shift + Down Arrow to select ever cell in that column.
Then, right-click on any of the selected cells and choose "Fill Down".
That will change the state of each checkbox to match the state of the first cell in the selection.

No, you do not need to do Refine > Reintegrate after changing the quantitative status of transitions. Skyline will automatically recalculate all numbers that depend on which transitions are quantitative.

Typically, you use the "Reimport" button on the "Edit > Manage Results" dialog when you make a change to a setting which affects chromatogram extraction, such as most of the settings on the "Full Scan" tab at "Settings > Transition Settings".

Refine > Reintegrate is usually used when you have a trained peak scoring model which is different from Skyline's default scoring model.
The other thing that you can use "Refine > Reintegrate" for is if you have manually adjusted a bunch of peaks and you want to throw away all those manual adjustments and get back to the state that things were in right after Skyline finished extracting chromatograms. To undo all manual peak adjustments you go to "Refine > Reintegrate" and choose "Default" as the Peak scoring model, and check the "Overwrite manual integration" is checked.

But, I can't think of any case where "Reintegrate" would have any effect after changing settings. You might have been thinking of "Reimport" on the "Manage Results" dialog which you use if you make a change that affects chromatogram extraction. There are some cases where you can get away with using the "Rescore" button on the Manage Results if the change affects peak scoring but not chromatogram extraction, such as spectral-library related changes.
But, "Reimport" is the usual button you use when you change settings.
But nothing like that is necessary when you change the quantitative status of transitions because that does not affect Skyline's opinion of peaks.
-- Nick

-- Nick

Thanks Nick, that's exactly what I was looking for.

In practice this seems to work on relatively small Skyline docs but not large ones. I'm working with a document with on the order of 10 million transitions, and attempting to mark millions of transitions as non-quantitative via this method crashes Skyline entirely. I can't figure out a workaround outside of downsampling to a much smaller Skyline doc.

Can you send me your Skyline document as well as the definition for the report that you are using to decide which transitions to mark as non-quantitative?
You can add the report definition to your Skyline document by going to the "Reports" tab at "Settings > Document Settings" and checking the checkbox next to the report name.

Then, you can use the menu item:
File > Share
to create a .zip file containing your Skyline document and supporting files including extracted chromatograms.

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

The Document Grid usually only needs to calculate the results for the screenful of data that you are looking at, but, in order for Skyline to answer the question of which cells in the Document Grid are selected, every row in that grid needs to come into existence. This could potentially require a lot of memory.
If your report is showing one row per Transition and Replicate, then it would have been nice if you were able to use the Pivot Editor to reduce the number of rows down to just one row per Transition. Unfortunately, in current versions of Skyline, cells pivoted reports are always read-only.
The next version of Skyline will support changing the values in some cells in pivoted reports.
You can learn more about the pivot editor here:
https://skyline.ms/wiki/home/software/Skyline/page.view?name=PivotEditor

Whenever we hear about huge Skyline documents that are causing performance problems, it is always very helpful for us to see those documents because we nearly always find easy things that we can do to reduce Skyline's memory requirements.
-- Nick

Ok, I uploaded to the file sharing folder with the name TRX-nettle.sky. I'm trying to export `transition-report`; I tried to add this into the Skyline doc. Definitely curious if there are less memory-intensive ways to accomplish this!

You can download a special version of Skyline from here:
https://proteome.gs.washington.edu/~nicksh/SpecialSkylines/PivotEditorPreview/

Because this is not an official build of Skyline, it has not been signed. Windows will try to prevent you from running it so you may need to hunt around for the "More Info" and "Run Anyway" buttons.

This special build of Skyline makes some columns editable even in a pivoted report.

What that means is, for instance, if you wanted to mark all of the transitions non-quantitative where at least one replicate had a Shape Correlation below a certain value, you could create a pivoted report with one row per Transition and another column which was the minimum value of Shape Correlation across all of the replicates.

This report would have only one row per Transition instead of one row per Transition and Replicate, so, for your dataset it would have 500,000 rows instead of 50 million.
The report still takes a while to run, but you would probably be able to mark all the Transitions you want non-quantitative in under an hour.

I have attached a pivoted report that I made. This report will only work with the special Pivot Editor Preview build of Skyline because it makes use of a new aggregate function "Median" which does not exist yet in regular Skyline.

You can learn more about pivoted reports here:
https://skyline.ms/wiki/home/software/Skyline/page.view?name=PivotEditor

-- Nick

Thanks, but I still can't figure this out. Are you gonna be at ASMS next week? Any chance we could work on this in person? My guess is there's something pretty simple that I can't figure out how to do.