Organ Mapping Antibody Panels: a community resource for standardized multiplexed tissue imaging.

Multiplexed antibody-based imaging enables the detailed characterization of molecular and cellular organization in tissues. Advances in the field now allow high-parameter data collection (>60 targets); however, considerable expertise and capital are needed to construct the antibody panels employed by these methods. Organ mapping antibody panels are community-validated resources that save time and money, increase reproducibility, accelerate discovery and support the construction of a Human Reference Atlas.

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.

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.

Scientific progress despite irreproducibility: A seeming paradox.

It appears paradoxical that science is producing outstanding new results and theories at a rapid rate at the same time that researchers are identifying serious problems in the practice of science that cause many reports to be irreproducible and invalid. Certainly, the practice of science needs to be improved, and scientists are now pursuing this goal. However, in this perspective, we argue that this seeming paradox is not new, has always been part of the way science works, and likely will remain so. We first introduce the paradox. We then review a wide range of challenges that appear to make scientific success difficult. Next, we describe the factors that make science work-in the past, present, and presumably also in the future. We then suggest that remedies for the present practice of science need to be applied selectively so as not to slow progress and illustrate with a few examples. We conclude with arguments that communication of science needs to emphasize not just problems but the enormous successes and benefits that science has brought and is now bringing to all elements of modern society.

Skill discrepancies between research, education, and jobs reveal the critical need to supply soft skills for the data economy.

Rapid research progress in science and technology (S&T) and continuously shifting workforce needs exert pressure on each other and on the educational and training systems that link them. Higher education institutions aim to equip new generations of students with skills and expertise relevant to workforce participation for decades to come, but their offerings sometimes misalign with commercial needs and new techniques forged at the frontiers of research. Here, we analyze and visualize the dynamic skill (mis-)alignment between academic push, industry pull, and educational offerings, paying special attention to the rapidly emerging areas of data science and data engineering (DS/DE). The visualizations and computational models presented here can help key decision makers understand the evolving structure of skills so that they can craft educational programs that serve workforce needs. Our study uses millions of publications, course syllabi, and job advertisements published between 2010 and 2016. We show how courses mediate between research and jobs. We also discover responsiveness in the academic, educational, and industrial system in how skill demands from industry are as likely to drive skill attention in research as the converse. Finally, we reveal the increasing importance of uniquely human skills, such as communication, negotiation, and persuasion. These skills are currently underexamined in research and undersupplied through education for the labor market. In an increasingly data-driven economy, the demand for "soft" social skills, like teamwork and communication, increase with greater demand for "hard" technical skills and tools.

Publication, funding, and experimental data in support of Human Reference Atlas construction and usage.

Experts from 18 consortia are collaborating on the Human Reference Atlas (HRA) which aims to map the 37 trillion cells in the healthy human body. Information relevant for HRA construction and usage is held by experts, published in scholarly papers, and captured in experimental data. However, these data sources use different metadata schemas and cannot be cross-searched efficiently. This paper documents the compilation of a dataset, named HRAlit, that links the 136 HRA v1.4 digital objects (31 organs with 4,279 anatomical structures, 1,210 cell types, 2,089 biomarkers) to 583,117 experts; 7,103,180 publications; 896,680 funded projects, and 1,816 experimental datasets. The resulting HRAlit has 22 tables with 20,939,937 records including 6 junction tables with 13,170,651 relationships. The HRAlit can be mined to identify leading experts, major papers, funding trends, or alignment with existing ontologies in support of systematic HRA construction and usage.

Interactive network visualization of opioid crisis research: a tool for reinforcing data linkage skills for public health policy researchers.

Background: Public health policy researchers face a persistent challenge in identifying and integrating relevant data, particularly in the context of the U.S. opioid crisis, where a comprehensive approach is crucial. Purpose: To meet this new workforce demand health policy and health economics programs are increasingly introducing data analysis and data visualization skills. Such skills facilitate data integration and discovery by linking multiple resources. Common linking strategies include individual or aggregate level linking (e.g., patient identifiers) in primary clinical data and conceptual linking (e.g., healthcare workforce, state funding, burnout rates) in secondary data. Often, the combination of primary and secondary datasets is sought, requiring additional skills, for example, understanding metadata and constructing interlinkages. Methods: To help improve those skills, we developed a 2-step process using a scoping method to discover data and network visualization to interlink metadata. Results: We show how these new skills enable the discovery of relationships among data sources pertinent to public policy research related to the opioid overdose crisis and facilitate inquiry across heterogeneous data resources. In addition, our interactive network visualization introduces (1) a conceptual approach, drawing from recent systematic review studies and linked by the publications, and (2) an aggregate approach, constructed using publicly available datasets and linked through crosswalks. Conclusions: These novel metadata visualization techniques can be used as a teaching tool or a discovery method and can also be extended to other public policy domains.

A Scalable Method for Readable Tree Layouts.

Large tree structures are ubiquitous and real-world relational datasets often have information associated with nodes (e.g., labels or other attributes) and edges (e.g., weights or distances) that need to be communicated to the viewers. Yet, scalable, easy to read tree layouts are difficult to achieve. We consider tree layouts to be readable if they meet some basic requirements: node labels should not overlap, edges should not cross, edge lengths should be preserved, and the output should be compact. There are many algorithms for drawing trees, although very few take node labels or edge lengths into account, and none optimizes all requirements above. With this in mind, we propose a new scalable method for readable tree layouts. The algorithm guarantees that the layout has no edge crossings and no label overlaps, and optimizes one of the remaining aspects: desired edge lengths and compactness. We evaluate the performance of the new algorithm by comparison with related earlier approaches using several real-world datasets, ranging from a few thousand nodes to hundreds of thousands of nodes. Tree layout algorithms can be used to visualize large general graphs, by extracting a hierarchy of progressively larger trees. We illustrate this functionality by presenting several map-like visualizations generated by the new tree layout algorithm.

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. 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.

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 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 statuses. 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.

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 .

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.

Understanding Contexts and Challenges of Information Management for Epilepsy Care.

Epilepsy is a common chronic neurological disease. People with epilepsy (PWE) and their caregivers face several challenges related to their epilepsy management, including quality of care, care coordination, side effects, and stigma management. The sociotechnical issues of the information management contexts and challenges for epilepsy care may be mitigated through effective information management. We conducted 4 focus groups with 5 PWE and 7 caregivers to explore how they manage epilepsy-related information and the challenges they encountered. Primary issues include challenges of finding the right information, complexities of tracking and monitoring data, and limited information sharing. We provide a framework that encompasses three attributes - individual epilepsy symptoms and health conditions, information complexity, and circumstantial constraints. We suggest future design implications to mitigate these challenges and improve epilepsy information management and care coordination.

Opioid Prescriptions Prior to Emergency Department Dental Visits: A Comparison of Dental Health Professional Shortage Areas (DPSAs) and Non-DPSAs Using Electronic Health Records.

Although prior research has linked dental conditions and opioid prescribing in the U.S., it is not yet known whether the receipt of opioid prescriptions prior to seeking emergency care for dental conditions differs in geographical areas that are underserved by health care professionals (Dental Professional Shortage Areas, DPSAs) compared to other areas. Using Indiana's state-wide electronic health records from January 1, 2016 to October 31, 2020, we examine if patients from DPSAs presenting at the emergency department (ED) for dental conditions are more likely to have received opioid prescriptions in the 30 days prior to their visit, compared to patients from other areas. A higher rate of opioid receipt among DPSA individuals may indicate an association between lower availability of dental professionals and the use of opioids as a coping strategy. We note that our study design has several limitations (such as a lack of data on prescription use after the ED visit) and does not prove causation. We find that individuals experiencing dental condition ED visits in DPSAs are 16% more likely (than those in non-DPSAs) to have filled an opioid prescription in the 30 days prior to the ED visit, after controlling for age, gender, and race/ethnicity. This result is statistically significant at the 1% level. The baseline rate of opioid filling in the 30 days prior to the ED visit is 12% in DPSAs. These correlational results suggest that unmet dental needs might be substantially connected to opioid prescriptions, although further research is needed to establish whether this relationship is causal.

Segmenting functional tissue units across human organs using community-driven development of generalizable machine learning algorithms.

The development of a reference atlas of the healthy human body requires automated image segmentation of major anatomical structures across multiple organs based on spatial bioimages generated from various sources with differences in sample preparation. We present the setup and results of the "Hacking the Human Body" machine learning algorithm development competition hosted by the Human Biomolecular Atlas (HuBMAP) and the Human Protein Atlas (HPA) teams on the Kaggle platform. We showcase how 1,175 teams from 78 countries engaged in community- driven, open-science code development that resulted in machine learning models which successfully segment anatomical structures across five organs using histology images from two consortia and that will be productized in the HuBMAP data portal to process large datasets at scale in support of Human Reference Atlas construction. We discuss the benchmark data created for the competition, major challenges faced by the participants, and the winning models and strategies.

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.