this is a rabbit hole that can go pretty deep... there are actually a couple of well known programs for generating layouts, that let you optimize the layout based on your corpus..This(1) is probably a good place to start. I believe these(2)(3) are some of the more commonly used tools, though its been a while since I looked.

1: http://xahlee.info/kbd/keyboard_layout_keybinding.html

2: http://mkweb.bcgsc.ca/carpalx/?readme

3: http://www.michaelcapewell.com/programming/keyboardevolve.ht...