Specimen, Biological Structure, and Spatial Ontologies in Support of a Human Reference Atlas

The Human Reference Atlas (HRA) is defined as a comprehensive, three-dimensional (3D) atlas of all the cells in the healthy human body. It is compiled by an international team of experts that develop standard terminologies linked to 3D reference objects describing anatomical structures. The third HRA release (v1.2) covers spatial reference data and ontology annotations for 26 organs. Experts access the HRA annotations via spreadsheets and view reference models in 3D editing tools. This paper introduces the Common Coordinate Framework Ontology (CCFO) v2.0.1 that interlinks specimen, biological structure, and spatial data together with the CCF API which makes the HRA programmatically accessible and interoperable with Linked Open Data (LOD). We detail how real-world user needs and experimental data guide CCFO design and implementation, present CCFO classes and properties together with examples of their usage, and report on technical validation performed. The CCFO graph database and API are used in the HuBMAP portal, Virtual Reality Organ Gallery, and other applications that support data queries across multiple, heterogeneous sources.