Toilet in spare bath runs automatically for 2 seconds about every 20 min!
The only possible cause is a slow leak.  There could be leaks in several places:


Flapper valve:   Did you replace the flapper?  Did you clean the flapper valve seat?  Run your finger all the way around it to feel for deposits and nicks.  Repair with light use of sandpaper.
Tank bolts:  These fasten the tank to the bowl unit.  If these were to leak, most toilets would weep water over the backside of the bowl housing onto the floor.  Check for moisture back there and all around on the floor.  Some toilets can weep here but direct water into the bowl.  The only way to discover this is by taking the bolts out and checking whether the bolt head seals are in good condition.
Inlet seal:  Where the water enters the tank from underneath is another area where gaskets prevent water from exiting the tank and weeping down the water line.  Check for moisture here.