Hi @biojack ,
I recommend reading the papers that I suggested here. Especially the first, which describes a few metrics for this specific problem, both distance metrics and qualitative (presence-absence) based tests:
We also have a plugin to do this exact evaluation already (q2-quality-control). See the docs on the QIIME 2 website for some usage examples (there are also some tutorials in the "community tutorials" section of this forum with examples, e.g., using fungal data).
I think you maybe mentioned in a previous thread that you want to do this test to compare different reference databases? Is that correct? In that case we have some additional methods for such database evaluations in RESCRIPt, and a benchmark of several different databases in this paper:
Good luck!