Compiling, Validating, and Using Human Reference Atlas Cell Type Annotation Crosswalks

The Human Reference Atlas (HRA) v2.5 includes 4,807 anatomical structures, 1,347 cell types, and 2,215 biomarkers (genes, proteins, lipids); 81 organs with 1,392 anatomical structures modeled in three dimensions (3D). Mapping new data into the HRA requires 3D spatial registration and/or cell type annotation (CTann). Many CTann tools exist but few use cell type names linked to Cell Ontology (CL)—making comparisons across tools, tissues, and organs difficult. The HRA supports five transcriptomics CTann tools (Azimuth, CellTypist, popV, FR-Match, Pan-Human Azimuth), four sc-proteomics CTann tools (DeepCell Types, DeepCell Types-HuBMAP, Robust Image-Based Cell Annotator [RIBCA], and SpaTial cELl LeARning [STELLAR]), plus a Cell Distance Explorer (CDE) Spatial Omics collection covering previously published annotations across 12 tissue types with 47,349,496 cells. Assigned cell types differ in number, resolution, and coverage. This paper details how 10 crosswalks were constructed, validated, and used to compile a ‘Supertree’ that can be used to compare CTann across organs and technologies in support of reference atlas constitution and usage. All data and code can be accessed at https://cns-iu.github.io/hra-ctann-supporting-information.