What methods should we implement to detect malicious content?

TUF and in-toto should go a long way to solve this problem. To use a pharmaceutical drug analogy, in-toto is the tool tells you who made which ingredients, and how they were all put together, whereas TUF is the tool that tells you who to trust in the first place, wraps it all up, and delivers them in a trustworthy seal.

Disclosure: I am involved with both projects.

Cc @JustinCappos