With the Information from https://en.wikipedia.org/wiki/Letter_frequency which lists the frequency of usage of Letters in the English language, I have made the first draft of a keyboard layout for such a keyboard.
The Idea is to have a space key which also acts as enter key if shift is pressed and 17 Symbol keys, which have 4 symbol layers. The Shift key is used by the thump. there are also 3 "layer keys". By default the keyboard assumes you want the Symbol of layer one. If you press the key for layer two or three the keyboard switches in the chosen one and uses the symbols from that layer. If you want back In layer one, press the key for the active layer again or that one for layer 4. Layer 4 is somewhat special.
As you can see in the picture, all the modifier keys are in there. With that a mean the ones which usually aren't pressed alone but with other keys. My idea was to only stay in layer 4 as long as the "L4" key is pressed. If you Ctrl and/or Alt until "L4" gets released, the keyboard shell switch into Layer one. Than it shall wait for the next symbol pressed and shall act like a normal keyboard if Ctrl and the Symbol are Pressed simultaneously. If you press Ctrl+Fn Some Similar combination or just Fn the key event shell be sent immediately. If you press "L4" alone and release it without pressing any symbol key, the keyboard shell fall back to layer one and forget about pressed modifier keys.
That's the idea, an implementation will follow, as soon as I have the hardware for it.