On some of the computers I support, our ClickOnce applications disappear (both from the desktop and the start menu) after restarting. These are applications that are designed to be run offline (they stay installed on the machine), and no other machines exhibit this problem.
After looking, it appears that the entire Users/AppData/Local/Apps folder is deleted after restarting. This is a remote client, and the machines this is happening to are all brand new running Windows 7. Since these are the only machines with the issue and they're all the same, I'm assuming that this is a Windows or user configuration issue rather than an application issue (since the application runs fine when it launches after installing), hence why I posted it here instead of on StackOverflow.
I've also noticed that on a couple of these machines, there is an additional user folder with .000 at the end of its name, if that points any fingers.