There are a growing number of reference ontologies available across a variety of biomedical domains and current research focuses on their construction, organization and use. An important use case for these ontologies is annotation—where users create metadata that access concepts and terms in reference ontologies. We draw on our experience in physiological modeling to present a compelling use case that demonstrates the potential complexity of such annotations. In the domain of physiological biosimulation, we argue that most annotations require the use of multiple reference ontologies. We suggest that these “composite” annotations should be retained as a repository of knowledge about post-coordination that promotes sharing and interoperation across biosimulation models
