You can mix up to a certain point (25-50%) without doing anything else and the fuel trims can compensate. That will solve any knock issues you have on an OTS map. You can't really take full advantage of it unless you also add timing to use that extra octane. The new Cobb ATR software has a global fuel scalar value that also allows compensating for the change in fuel mixture so now you can run 100% without fuel trim problems. Because a higher volume of fuel is required as you add E85, people with any fuel system issues will see their problems get much worse on E85, though.
I just put about 9 gallons of E85 in on an almost empty tank. I left room in the tank in case I had problems and had to add more gasoline. Ran for about 20 minutes and took a data log. No problems so far, but I can't look at the log until I get home.