A biomedical open knowledge network harnesses the power of AI to understand deep human biology.

Knowledge representation and reasoning (KR&R) has been successfully implemented in many fields to enable computers to solve complex problems with AI methods. However, its application to biomedicine has been lagging in part due to the daunting complexity of molecular and cellular pathways that govern human physiology and pathology. In this article we describe concrete uses of SPOKE, an open knowledge network that connects curated information from 37 specialized and human-curated databases into a single property graph, with 3 million nodes and 15 million edges to date. Applications discussed in this article include drug discovery, COVID-19 research and chronic disease diagnosis and management.

Visual Analytics for Data-Driven Understanding of the Substance Use Disorder Epidemic.

The substance use disorder epidemic has emerged as a serious public health crisis, presenting complex challenges. Visual analytics offers a unique approach to address this complexity and facilitate effective interventions. This paper details the development of an innovative visual analytics dashboard, aimed at enhancing our understanding of the substance use disorder epidemic. By employing record linkage techniques, we integrate diverse data sources to provide a comprehensive view of the epidemic. Adherence to responsive, open, and user-centered design principles ensures the dashboard's usefulness and usability. Our approach to data and design encourages collaboration among various stakeholders, including researchers, politicians, and healthcare practitioners. Through illustrative outputs, we demonstrate how the dashboard can deepen our understanding of the epidemic, support intervention strategies, and evaluate the effectiveness of implemented measures. The paper concludes with a discussion of the dashboard's use cases and limitations.

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 and 2D/3D reference objects. New experimental data can be mapped into the HRA using (1) three cell type annotation tools (e.g., Azimuth) or (2) validated antibody panels (OMAPs), or (3) by registering tissue data spatially. 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 previews atlas usage applications.

Ontology-based modeling, integration, and analysis of heterogeneous clinical, pathological, and molecular kidney data for precision medicine.

Many data resources generate, process, store, or provide kidney related molecular, pathological, and clinical data. Reference ontologies offer an opportunity to support knowledge and data integration. The Kidney Precision Medicine Project (KPMP) team contributed to the representation and addition of 329 kidney phenotype terms to the Human Phenotype Ontology (HPO), and identified many subcategories of acute kidney injury (AKI) or chronic kidney disease (CKD). The Kidney Tissue Atlas Ontology (KTAO) imports and integrates kidney-related terms from existing ontologies (e.g., HPO, CL, and Uberon) and represents 259 kidney-related biomarkers. We have also developed a precision medicine metadata ontology (PMMO) to integrate 50 variables from KPMP and CZ CellxGene data resources and applied PMMO for integrative kidney data analysis. The gene expression profiles of kidney gene biomarkers were specifically analyzed under healthy control or AKI/CKD disease states. This work demonstrates how ontology-based approaches support multi-domain data and knowledge integration in precision medicine.

Introducing the open biomedical map of science.

This article introduces work in progress to develop a new, open biomedical map of science (OBMS) using the PubMed citation database. The new science map represents bimodal network relationships between journals and medical subject heading (MeSH) descriptors, based on a journal's articles indexed in the MEDLINE component of PubMed. We review the current efforts to use PubMed data in science of science studies and science mapping. As part of the development process, we compare the journals indexed in PubMed with journals included in the 2011 UCSD map of science to establish a baseline of disciplinary coverage of PubMed for the period 2009-2019. Journal article frequency is analyzed to establish the minimum number of citations required by a journal for inclusion in a map of science. A prototype OBMS is presented, and we discuss the strengths and weaknesses of the OBMS, as well as the next steps for using and productizing this new open map for general and free usage.

Anatomical structures, cell types, and biomarkers of the healthy human blood vasculature.

More than 150 scientists from 17 consortia are collaborating on an international project to build a Human Reference Atlas, which maps all 37 trillion cells in the healthy adult human body. The initial release of this atlas provided hierarchical lists of the anatomical structures, cell types, and biomarkers in 11 organs. Here, we describe the methods we used as part of this initiative to build the first open, computer-readable, and comprehensive database of the adult human blood vasculature, called the Human Reference Atlas-Vasculature Common Coordinate Framework (HRA-VCCF). It includes 993 vessels and their branching connections, 10 cell types, and 10 biomarkers. With this paper we are releasing additional details on vessel types and subtypes, branching sequence, anastomoses, portal systems, microvasculature, functional tissue units, mappings to regions vessels supply or drain, geometric properties of vessels, and links to 3D reference objects. Future versions will add variants and connections to the lymph vasculature; and, it will iteratively expand and improve the database as additional experimental data become available through the participating consortia.

Functional Tissue Units in the Human Reference Atlas.

Functional tissue units (FTUs) form the basic building blocks of organs and are important for understanding and modeling the healthy physiological function of the organ and changes during disease states. In this first comprehensive catalog of FTUs, we document the definition, physical dimensions, vasculature, and cellular composition of 22 anatomically correct, nested functional tissue units (FTUs) in 10 healthy human organs. The catalog includes datasets, illustrations, an interactive online FTU explorer, and a large printable poster. All data and code are freely available. This is part of a larger ongoing international effort to construct a Human Reference Atlas (HRA) of all cells in the human body.

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.

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.

"Then and Now," Mapping the 25 Year Evolution and Impact of North American Vascular Biology Organization Science Through Publications of its Founding and Current Members.

Scholarly organizations bring together experts to move forward specific areas of scientific endeavor. More than 5,000 scholarly societies exist world-wide yet little is known about the composition, evolution, and collaboration of experts within these organizations. This study presents general methods to study the evolution of a biomedical organization and its impact over time. Methods are illustrated in a case study that aims to capture the "Then and Now" science of the North American Vascular Biology Organization (NAVBO). Publications authored by the founding members who came together to create NAVBO in 1994 are compared with publications by those representing the society 25 years later. Google Scholar data was compiled for NAVBO members registered in 1994 (n = 70) and in 2019 (n = 465), some members being present in both data sets (n = 22). The 501 unique NAVBO members had more than 76,000 papers cited over 4,400,000 times. Several characteristics associated with the NAVBO members' output were revealed, including their high productivity, the high impact of their publications, and the predominant contribution of relatively small laboratories, as suggested by a low average number of authors per publication. To understand how NAVBO fostered scientific collaborations and exchanges of expertize, data was analyzed and visualized to show the evolution of member co-author networks. The UCSD Map of Science was used to communicate the evolution of scientific topics covered by NAVBO members helping to create a global picture of NAVBO's science "then and now." All workflows are available online in case other scholarly organizations would want to use them to map their own evolution and impact; and meta studies that communicate the inner workings of these important scholarly efforts can be conducted.

Designing highly flexible and usable cyberinfrastructures for convergence.

This article presents the results of a 7-year-long quest into the development of a "dream tool" for our research in information science and scientometrics and more recently, network science. The results are two cyberinfrastructures (CI): The Cyberinfrastructure for Information Visualization and the Network Workbench that enjoy a growing national and interdisciplinary user community. Both CIs use the cyberinfrastructure shell (CIShell) software specification, which defines interfaces between data sets and algorithms/services and provides a means to bundle them into powerful tools and (Web) services. In fact, CIShell might be our major contribution to progress in convergence. Just as Wikipedia is an "empty shell" that empowers lay persons to share text, a CIShell implementation is an "empty shell" that empowers user communities to plug-and-play, share, compare and combine data sets, algorithms, and compute resources across national and disciplinary boundaries. It is argued here that CIs will not only transform the way science is conducted but also will play a major role in the diffusion of expertise, data sets, algorithms, and technologies across multiple disciplines and business sectors leading to a more integrative science.