Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas Construction and Usage.

The Human BioMolecular Atlas Program (HuBMAP) aims to construct a reference 3D structural, cellular, and molecular atlas of the healthy adult human body. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) serves experimental datasets and supports data processing, search, filtering, and visualization. The Human Reference Atlas (HRA) Portal (https://humanatlas.io) provides open access to atlas data, code, procedures, and instructional materials. Experts from more than 20 consortia are collaborating to construct the HRA's Common Coordinate Framework (CCF), knowledge graphs, and tools that describe the multiscale structure of the human body (from organs and tissues down to cells, genes, and biomarkers) and to use the HRA to understand changes that occur at each of these levels with aging, disease, and other perturbations. The 6th release of the HRA v2.0 covers 36 organs with 4,499 unique anatomical structures, 1,195 cell types, and 2,089 biomarkers (e.g., genes, proteins, lipids) linked to ontologies. In addition, three workflows were developed to map new experimental data into the HRA's CCF. This paper describes the HRA user stories, terminology, data formats, ontology validation, unified analysis workflows, user interfaces, instructional materials, application programming interface (APIs), flexible hybrid cloud infrastructure, and demonstrates first atlas usage applications and previews.

Segmentation of human functional tissue units in support of a Human Reference Atlas.

The Human BioMolecular Atlas Program (HuBMAP) aims to compile a Human Reference Atlas (HRA) for the healthy adult body at the cellular level. Functional tissue units (FTUs), relevant for HRA construction, are of pathobiological significance. Manual segmentation of FTUs does not scale; highly accurate and performant, open-source machine-learning algorithms are needed. We designed and hosted a Kaggle competition that focused on development of such algorithms and 1200 teams from 60 countries participated. We present the competition outcomes and an expanded analysis of the winning algorithms on additional kidney and colon tissue data, and conduct a pilot study to understand spatial location and density of FTUs across the kidney. The top algorithm from the competition, Tom, outperforms other algorithms in the expanded study, while using fewer computational resources. Tom was added to the HuBMAP infrastructure to run kidney FTU segmentation at scale-showcasing the value of Kaggle competitions for advancing research.

The HRA Organ Gallery affords immersive superpowers for building and exploring the Human Reference Atlas with virtual reality.

The Human Reference Atlas (HRA, https://humanatlas.io) funded by the NIH Human Biomolecular Atlas Program (HuBMAP, https://commonfund.nih.gov/hubmap) and other projects engages 17 international consortia to create a spatial reference of the healthy adult human body at single-cell resolution. The specimen, biological structure, and spatial data that define the HRA are disparate in nature and benefit from a visually explicit method of data integration. Virtual reality (VR) offers unique means to enable users to explore complex data structures in a three-dimensional (3D) immersive environment. On a 2D desktop application, the 3D spatiality and real-world size of the 3D reference organs of the atlas is hard to understand. If viewed in VR, the spatiality of the organs and tissue blocks mapped to the HRA can be explored in their true size and in a way that goes beyond traditional 2D user interfaces. Added 2D and 3D visualizations can then provide data-rich context. In this paper, we present the HRA Organ Gallery, a VR application to explore the atlas in an integrated VR environment. Presently, the HRA Organ Gallery features 55 3D reference organs, 1,203 mapped tissue blocks from 292 demographically diverse donors and 15 providers that link to 6,000+ datasets; it also features prototype visualizations of cell type distributions and 3D protein structures. We outline our plans to support two biological use cases: on-ramping novice and expert users to HuBMAP data available via the Data Portal (https://portal.hubmapconsortium.org), and quality assurance/quality control (QA/QC) for HRA data providers. Code and onboarding materials are available at https://github.com/cns-iu/hra-organ-gallery-in-vr.

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 who develop standard terminologies that they link 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 object models in 3D editing tools. This paper introduces the Common Coordinate Framework (CCF) Ontology v2.0.1 that interlinks specimen, biological structure, and spatial data, together with the CCF API that makes the HRA programmatically accessible and interoperable with Linked Open Data (LOD). We detail how real-world user needs and experimental data guide CCF Ontology design and implementation, present CCF Ontology classes and properties together with exemplary usage, and report on validation methods. The CCF Ontology graph database and API are used in the HuBMAP portal, HRA Organ Gallery, and other applications that support data queries across multiple, heterogeneous sources.

The HRA Organ Gallery Affords Immersive Superpowers for Building and Exploring the Human Reference Atlas with Virtual Reality.

The Human Reference Atlas (HRA, https://humanatlas.io ) funded by the NIH Human Biomolecular Atlas Program (HuBMAP, https://commonfund.nih.gov/hubmap ) and other projects engages 17 international consortia to create a spatial reference of the healthy adult human body at single-cell resolution. The specimen, biological structure, and spatial data that define the HRA are disparate in nature and benefit from a visually explicit method of data integration. Virtual reality (VR) offers unique means to enable users to explore complex data structures in a threedimensional (3D) immersive environment. On a 2D desktop application, the 3D spatiality and real-world size of the 3D reference organs of the atlas is hard to understand. If viewed in VR, the spatiality of the organs and tissue blocks mapped to the HRA can be explored in their true size and in a way that goes beyond traditional 2D user interfaces. Added 2D and 3D visualizations can then provide data-rich context. In this paper, we present the HRA Organ Gallery, a VR application to explore the atlas in an integrated VR environment. Presently, the HRA Organ Gallery features 55 3D reference organs,1,203 mapped tissue blocks from 292 demographically diverse donors and 15 providers that link to 5,000+ datasets; it also features prototype visualizations of cell type distributions and 3D protein structures. We outline our plans to support two biological use cases: on-ramping novice and expert users to HuBMAP data available via the Data Portal ( https://portal.hubmapconsortium.org ), and quality assurance/quality control (QA/QC) for HRA data providers . Code and onboarding materials are available at https://github.com/cns-iu/ccf-organ-vr-gallery#readme .

Tissue registration and exploration user interfaces in support of a human reference atlas.

Seventeen international consortia are collaborating on a human reference atlas (HRA), a comprehensive, high-resolution, three-dimensional atlas of all the cells in the healthy human body. Laboratories around the world are collecting tissue specimens from donors varying in sex, age, ethnicity, and body mass index. However, harmonizing tissue data across 25 organs and more than 15 bulk and spatial single-cell assay types poses challenges. Here, we present software tools and user interfaces developed to spatially and semantically annotate ("register") and explore the tissue data and the evolving HRA. A key part of these tools is a common coordinate framework, providing standard terminologies and data structures for describing specimen, biological structure, and spatial data linked to existing ontologies. As of April 22, 2022, the "registration" user interface has been used to harmonize and publish data on 5,909 tissue blocks collected by the Human Biomolecular Atlas Program (HuBMAP), the Stimulating Peripheral Activity to Relieve Conditions program (SPARC), the Human Cell Atlas (HCA), the Kidney Precision Medicine Project (KPMP), and the Genotype Tissue Expression project (GTEx). Further, 5,856 tissue sections were derived from 506 HuBMAP tissue blocks. The second "exploration" user interface enables consortia to evaluate data quality, explore tissue data spatially within the context of the HRA, and guide data acquisition. A companion website is at https://cns-iu.github.io/HRA-supporting-information/ .

Anatomical structures, cell types and biomarkers of the Human Reference Atlas.

The Human Reference Atlas (HRA) aims to map all of the cells of the human body to advance biomedical research and clinical practice. This Perspective presents collaborative work by members of 16 international consortia on two essential and interlinked parts of the HRA: (1) three-dimensional representations of anatomy that are linked to (2) tables that name and interlink major anatomical structures, cell types, plus biomarkers (ASCT+B). We discuss four examples that demonstrate the practical utility of the HRA.

3D virtual reality vs. 2D desktop registration user interface comparison.

Working with organs and extracted tissue blocks is an essential task in many medical surgery and anatomy environments. In order to prepare specimens from human donors for further analysis, wet-bench workers must properly dissect human tissue and collect metadata for downstream analysis, including information about the spatial origin of tissue. The Registration User Interface (RUI) was developed to allow stakeholders in the Human Biomolecular Atlas Program (HuBMAP) to register tissue blocks-i.e., to record the size, position, and orientation of human tissue data with regard to reference organs. The RUI has been used by tissue mapping centers across the HuBMAP consortium to register a total of 45 kidney, spleen, and colon tissue blocks, with planned support for 17 organs in the near future. In this paper, we compare three setups for registering one 3D tissue block object to another 3D reference organ (target) object. The first setup is a 2D Desktop implementation featuring a traditional screen, mouse, and keyboard interface. The remaining setups are both virtual reality (VR) versions of the RUI: VR Tabletop, where users sit at a physical desk which is replicated in virtual space; VR Standup, where users stand upright while performing their tasks. All three setups were implemented using the Unity game engine. We then ran a user study for these three setups involving 42 human subjects completing 14 increasingly difficult and then 30 identical tasks in sequence and reporting position accuracy, rotation accuracy, completion time, and satisfaction. All study materials were made available in support of future study replication, alongside videos documenting our setups. We found that while VR Tabletop and VR Standup users are about three times as fast and about a third more accurate in terms of rotation than 2D Desktop users (for the sequence of 30 identical tasks), there are no significant differences between the three setups for position accuracy when normalized by the height of the virtual kidney across setups. When extrapolating from the 2D Desktop setup with a 113-mm-tall kidney, the absolute performance values for the 2D Desktop version (22.6 seconds per task, 5.88 degrees rotation, and 1.32 mm position accuracy after 8.3 tasks in the series of 30 identical tasks) confirm that the 2D Desktop interface is well-suited for allowing users in HuBMAP to register tissue blocks at a speed and accuracy that meets the needs of experts performing tissue dissection. In addition, the 2D Desktop setup is cheaper, easier to learn, and more practical for wet-bench environments than the VR setups.

Data visualization literacy: Definitions, conceptual frameworks, exercises, and assessments.

In the information age, the ability to read and construct data visualizations becomes as important as the ability to read and write text. However, while standard definitions and theoretical frameworks to teach and assess textual, mathematical, and visual literacy exist, current data visualization literacy (DVL) definitions and frameworks are not comprehensive enough to guide the design of DVL teaching and assessment. This paper introduces a data visualization literacy framework (DVL-FW) that was specifically developed to define, teach, and assess DVL. The holistic DVL-FW promotes both the reading and construction of data visualizations, a pairing analogous to that of both reading and writing in textual literacy and understanding and applying in mathematical literacy. Specifically, the DVL-FW defines a hierarchical typology of core concepts and details the process steps that are required to extract insights from data. Advancing the state of the art, the DVL-FW interlinks theoretical and procedural knowledge and showcases how both can be combined to design curricula and assessment measures for DVL. Earlier versions of the DVL-FW have been used to teach DVL to more than 8,500 residential and online students, and results from this effort have helped revise and validate the DVL-FW presented here.

Science map metaphors: a comparison of network versus hexmap-based visualizations.

Most maps of science use a network layout; few use a landscape metaphor. Human users are trained in reading geospatial maps, yet most have a hard time reading even simple networks. Prior work using general networks has shown that map-based visualizations increase recall accuracy of data. This paper reports the result of a comparison of two comparable renderings of the UCSD map of science that are: the original network layout and a novel hexmap that uses a landscape metaphor to layout the 554 subdisciplines grouped into 13 color-coded disciplines of science. Overlaid are HITS metrics that show the impact and transformativeness of different scientific subdisciplines. Both maps support the same interactivity, including search, filter, zoom, panning, and details on demand. Users performed memorization, search, and retrieval tasks using both maps. Results did not show any significant differences in how the two maps were remembered or used by participants. We conclude with a discussion of results and planned future work.