The main disadvantage is query bias. The phenomenon that such databases are usually developed taking into account one particular type of request and are difficult to process when other requests need to be written.
Suppose you have Students and Courses, and you simulate all this so that you can say in one row in one table: "John Doe accepts {French, Algebra, Relational Theory}" and "Jane Doe accepts {German, functional computing , relational theory}. "
This makes it easy to request “all the courses that follow ...”, but try to imagine what it takes to answer the question “what are all the students who follow the relational theory”.
Try to imagine everything that the system itself should do to give such a request (if you could write) any chance for a reasonable execution ...
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