I like to think the Tyranids and maybe also necrons are invisible to the Emperor sight, in the same Navigators were invisible to Paul. Since in Dune someone with complete prescience can't see the life of someone else with priscience even if it is far weaker. Perhaps the Gold Path of the Emperor would have worked, humanity could have foguth off chaos and the other xenos threats. But he didn't account for the souless necrons and tyranids (in the sense they are hivemind and lack individuals and are souless per-se not literally).
Also I realised that Leto joined with a worm as his 'inhumane' transformation to led humanity. While the Emperor had to join with arcane DAOT tech and is equally an abomiantion, the loneliest person in excistence and trapped in his new form of corpse and metal.