Towards a Clinically-based Common Coordinate Framework for the Human Gut Cell Atlas - The Gut Models

Background The Human Cell Atlas resource will deliver single cell transcriptome data spatially organised in terms of gross anatomy, tissue location and with images of cellular histology. This will enable the application of bioinformatics analysis, machine learning and data mining revealing an atlas of cell types, sub-types, varying states and ultimately cellular changes related to disease conditions. To further develop the understanding of specific pathological and histopathological phenotypes with their spatial relationships and dependencies, a more sophisticated spatial descriptive framework is required to enable integration and analysis in spatial terms. Methods We describe a conceptual coordinate model for the Gut Cell Atlas (small and large intestines). Here, we focus on a Gut Linear Model (1-dimensional representation based on the centreline of the gut) that represents the location semantics as typically used by clinicians and pathologists when describing location in the gut. This knowledge representation is based on a set of standardised gut anatomy ontology terms describing regions in situ , such as ileum or transverse colon, and landmarks, such as ileo-caecal valve or hepatic flexure, together with relative or absolute distance measures. We show how locations in the 1D model can be mapped to and from points and regions in both a 2D model and 3D models, such as a patient’s CT scan where the gut has been segmented. Results The outputs of this work include 1D, 2D and 3D models of the human gut, delivered through publicly accessible Json and image files. We also illustrate the mappings between models using a demonstrator tool that allows the user to explore the anatomical space of the gut. All data and software is fully open-source and available online. Conclusions Small and large intestines have a natural “gut coordinate” system best represented as a 1D centreline through the gut tube, reflecting functional differences. Such a 1D centreline model with landmarks, visualised using viewer software allows interoperable translation to both a 2D anatomogram model and multiple 3D models of the intestines. This permits users to accurately locate samples for data comparison. ### Competing Interest Statement The authors have declared no competing interest. * ASCT+B : Anatomical Structures, Cell Types, plus Biomarkers BSPO : Biological Spatial Ontology CCF : Common Coordinate Framework CD : Crohn’s Disease CO : Cell Ontology CT : Computed Tomography EBI : European Bioinformatics Institute FMA : Foundational Model of Anatomy HCA : Human Cell Atlas HDBR : Human Developmental Biology Resource HGCA Human Gut Cell Atlas HuBMAP : Human BioMolecular Atlas Program IBD Inflammatory Bowel Disease ICV : Ileocaecal Valve JSON : JavaScript Object Notation MAST : Model-based Analysis of Single-cell Transcriptomics MRI : Magnetic Resonance Imaging MVC : Model-View-Controller OLS : Ontology Lookup Service PCA : Principal Component Analysis RNA : Ribonucleic Acid ROI : Region Of Interest SCA : Single Cell Analysis SCEA : Single Cell Expression Atlas t-SNE : t-distributed stochastic neighbour embedding UMAP : Uniform Manifold Approximation and Projection UMI : Unique Molecular Identifier