Big knowledge visualization of the COVID-19 CIDO ontology evolution.

BACKGROUND: The extensive international research for medications and vaccines for the devastating COVID-19 pandemic requires a standard reference ontology. Among the current COVID-19 ontologies, the Coronavirus Infectious Disease Ontology (CIDO) is the largest one. Furthermore, it keeps growing very frequently. Researchers using CIDO as a reference ontology, need a quick update about the content added in a recent release to know how relevant the new concepts are to their research needs. Although CIDO is only a medium size ontology, it is still a large knowledge base posing a challenge for a user interested in obtaining the "big picture" of content changes between releases. Both a theoretical framework and a proper visualization are required to provide such a "big picture". METHODS: The child-of-based layout of the weighted aggregate partial-area taxonomy summarization network (WAT) provides a "big picture" convenient visualization of the content of an ontology. In this paper we address the "big picture" of content changes between two releases of an ontology. We introduce a new DIFF framework named Diff Weighted Aggregate Taxonomy (DWAT) to display the differences between the WATs of two releases of an ontology. We use a layered approach which consists first of a DWAT of major subjects in CIDO, and then drill down a major subject of interest in the top-level DWAT to obtain a DWAT of secondary subjects and even further refined layers. RESULTS: A visualization of the Diff Weighted Aggregate Taxonomy is demonstrated on the CIDO ontology. The evolution of CIDO between 2020 and 2022 is demonstrated in two perspectives. Drilling down for a DWAT of secondary subject networks is also demonstrated. We illustrate how the DWAT of CIDO provides insight into its evolution. CONCLUSIONS: The new Diff Weighted Aggregate Taxonomy enables a layered approach to view the "big picture" of the changes in the content between two releases of an ontology.

Mining of EHR for interface terminology concepts for annotating EHRs of COVID patients.

BACKGROUND: Two years into the COVID-19 pandemic and with more than five million deaths worldwide, the healthcare establishment continues to struggle with every new wave of the pandemic resulting from a new coronavirus variant. Research has demonstrated that there are variations in the symptoms, and even in the order of symptom presentations, in COVID-19 patients infected by different SARS-CoV-2 variants (e.g., Alpha and Omicron). Textual data in the form of admission notes and physician notes in the Electronic Health Records (EHRs) is rich in information regarding the symptoms and their orders of presentation. Unstructured EHR data is often underutilized in research due to the lack of annotations that enable automatic extraction of useful information from the available extensive volumes of textual data. METHODS: We present the design of a COVID Interface Terminology (CIT), not just a generic COVID-19 terminology, but one serving a specific purpose of enabling automatic annotation of EHRs of COVID-19 patients. CIT was constructed by integrating existing COVID-related ontologies and mining additional fine granularity concepts from clinical notes. The iterative mining approach utilized the techniques of 'anchoring' and 'concatenation' to identify potential fine granularity concepts to be added to the CIT. We also tested the generalizability of our approach on a hold-out dataset and compared the annotation coverage to the coverage obtained for the dataset used to build the CIT. RESULTS: Our experiments demonstrate that this approach results in higher annotation coverage compared to existing ontologies such as SNOMED CT and Coronavirus Infectious Disease Ontology (CIDO). The final version of CIT achieved about 20% more coverage than SNOMED CT and 50% more coverage than CIDO. In the future, the concepts mined and added into CIT could be used as training data for machine learning models for mining even more concepts into CIT and further increasing the annotation coverage. CONCLUSION: In this paper, we demonstrated the construction of a COVID interface terminology that can be utilized for automatically annotating EHRs of COVID-19 patients. The techniques presented can identify frequently documented fine granularity concepts that are missing in other ontologies thereby increasing the annotation coverage.

A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology.

BACKGROUND: The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020. RESULTS: As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. CONCLUSION: CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications.

Risk Factors Associated With SARS-CoV-2 Breakthrough Infections in Fully mRNA-Vaccinated Individuals: Retrospective Analysis.

BACKGROUND: COVID-19 messenger RNA (mRNA) vaccines have demonstrated efficacy and effectiveness in preventing symptomatic COVID-19, while being relatively safe in trial studies. However, vaccine breakthrough infections have been reported. OBJECTIVE: This study aims to identify risk factors associated with COVID-19 breakthrough infections among fully mRNA-vaccinated individuals. METHODS: We conducted a series of observational retrospective analyses using the electronic health records (EHRs) of the Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York City (NYC) adult residences with at least 1 polymerase chain reaction (PCR) record were included in this analysis. Poisson regression was performed to assess the association between the breakthrough infection rate in vaccinated individuals and multiple risk factors-including vaccine brand, demographics, and underlying conditions-while adjusting for calendar month, prior number of visits, and observational days in the EHR. RESULTS: The overall estimated breakthrough infection rate was 0.16 (95% CI 0.14-0.18). Individuals who were vaccinated with Pfizer/BNT162b2 (incidence rate ratio [IRR] against Moderna/mRNA-1273=1.66, 95% CI 1.17-2.35) were male (IRR against female=1.47, 95% CI 1.11-1.94) and had compromised immune systems (IRR=1.48, 95% CI 1.09-2.00) were at the highest risk for breakthrough infections. Among all underlying conditions, those with primary immunodeficiency, a history of organ transplant, an active tumor, use of immunosuppressant medications, or Alzheimer disease were at the highest risk. CONCLUSIONS: Although we found both mRNA vaccines were effective, Moderna/mRNA-1273 had a lower incidence rate of breakthrough infections. Immunocompromised and male individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARS-CoV-2 pandemic, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.

Visual comprehension and orientation into the COVID-19 CIDO ontology.

The current intensive research on potential remedies and vaccinations for COVID-19 would greatly benefit from an ontology of standardized COVID terms. The Coronavirus Infectious Disease Ontology (CIDO) is the largest among several COVID ontologies, and it keeps growing, but it is still a medium sized ontology. Sophisticated CIDO users, who need more than searching for a specific concept, require orientation and comprehension of CIDO. In previous research, we designed a summarization network called "partial-area taxonomy" to support comprehension of ontologies. The partial-area taxonomy for CIDO is of smaller magnitude than CIDO, but is still too large for comprehension. We present here the "weighted aggregate taxonomy" of CIDO, designed to provide compact views at various granularities of our partial-area taxonomy (and the CIDO ontology). Such a compact view provides a "big picture" of the content of an ontology. In previous work, in the visualization patterns used for partial-area taxonomies, the nodes were arranged in levels according to the numbers of relationships of their concepts. Applying this visualization pattern to CIDO's weighted aggregate taxonomy resulted in an overly long and narrow layout that does not support orientation and comprehension since the names of nodes are barely readable. Thus, we introduce in this paper an innovative visualization of the weighted aggregate taxonomy for better orientation and comprehension of CIDO (and other ontologies). A measure for the efficiency of a layout is introduced and is used to demonstrate the advantage of the new layout over the previous one. With this new visualization, the user can "see the forest for the trees" of the ontology. Benefits of this visualization in highlighting insights into CIDO's content are provided. Generality of the new layout is demonstrated.