In single-species proteomics, protein databases are typically derived from well-characterized genomes. In metaproteomics, however, the organisms present in the sample may be unknown, and their genomes might not yet be available in public databases, making database construction more complex. Blakeley-Ruiz and Kleiner describe four main approaches for building metaproteomics databases, each with strengths and limitations: matched or unmatched metagenomes, and restricted or unrestricted reference databases (Figure ).