The National Institutes of Healths (NIH) Human Biomolecular Atlas Program (HuBMAP) aims to create a comprehensive high-resolution atlas of all the cells in the healthy human body. Multiple laboratories across the United States are collecting tissue specimens from different organs of donors who vary in sex, age, and body size. Integrating and harmonizing the data derived from these samples and mapping them into a common three-dimensional (3D) space is a major challenge. The key to making this possible is a Common Coordinate Framework (CCF), which provides a semantically annotated, 3D reference system for the entire body. The CCF enables contributors to HuBMAP to register specimens and datasets within a common spatial reference system, and it supports a standardized way to query and explore data in a spatially and semantically explicit manner. [...] This paper describes the construction and usage of a CCF for the human body and its reference implementation in HuBMAP. The CCF consists of (1) a CCF Clinical Ontology, which provides metadata about the specimen and donor (the who); (2) a CCF Semantic Ontology, which describes what part of the body a sample came from and details anatomical structures, cell types, and biomarkers (ASCT+B); and (3) a CCF Spatial Ontology, which indicates where a tissue sample is located in a 3D coordinate system. An initial version of all three CCF ontologies has been implemented for the first HuBMAP Portal release. It was successfully used by Tissue Mapping Centers to semantically annotate and spatially register 48 kidney and spleen tissue blocks. The blocks can be queried and explored in their clinical, semantic, and spatial context via the CCF user interface in the HuBMAP Portal.
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