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.

COVID-19Base v3: Update of the knowledgebase for drugs and biomedical entities linked to COVID-19.

COVID-19 has taken a huge toll on our lives over the last 3 years. Global initiatives put forward by all stakeholders are still in place to combat this pandemic and help us learn lessons for future ones. While the vaccine rollout was not able to curb the spread of the disease for all strains, the research community is still trying to develop effective therapeutics for COVID-19. Although Paxlovid and remdesivir have been approved by the FDA against COVID-19, they are not free of side effects. Therefore, the search for a therapeutic solution with high efficacy continues in the research community. To support this effort, in this latest version (v3) of COVID-19Base, we have summarized the biomedical entities linked to COVID-19 that have been highlighted in the scientific literature after the vaccine rollout. Eight different topic-specific dictionaries, i.e., gene, miRNA, lncRNA, PDB entries, disease, alternative medicines registered under clinical trials, drugs, and the side effects of drugs, were used to build this knowledgebase. We have introduced a BLSTM-based deep-learning model to predict the drug-disease associations that outperforms the existing model for the same purpose proposed in the earlier version of COVID-19Base. For the very first time, we have incorporated disease-gene, disease-miRNA, disease-lncRNA, and drug-PDB associations covering the largest number of biomedical entities related to COVID-19. We have provided examples of and insights into different biomedical entities covered in COVID-19Base to support the research community by incorporating all of these entities under a single platform to provide evidence-based support from the literature. COVID-19Base v3 can be accessed from: https://covidbase-v3.vercel.app/. The GitHub repository for the source code and data dictionaries is available to the community from: https://github.com/91Abdullah/covidbasev3.0.

Integrated multiomics analysis to infer COVID-19 biological insights.

Three years after the pandemic, we still have an imprecise comprehension of the pathogen landscape and we are left with an urgent need for early detection methods and effective therapy for severe COVID-19 patients. The implications of infection go beyond pulmonary damage since the virus hijacks the host's cellular machinery and consumes its resources. Here, we profiled the plasma proteome and metabolome of a cohort of 57 control and severe COVID-19 cases using high-resolution mass spectrometry. We analyzed their proteome and metabolome profiles with multiple depths and methodologies as conventional single omics analysis and other multi-omics integrative methods to obtain the most comprehensive method that portrays an in-depth molecular landscape of the disease. Our findings revealed that integrating the knowledge-based and statistical-based techniques (knowledge-statistical network) outperformed other methods not only on the pathway detection level but even on the number of features detected within pathways. The versatile usage of this approach could provide us with a better understanding of the molecular mechanisms behind any biological system and provide multi-dimensional therapeutic solutions by simultaneously targeting more than one pathogenic factor.

Curating a knowledge base for individuals with coinfection of HIV and SARS-CoV-2: a study protocol of EHR-based data mining and clinical implementation.

INTRODUCTION: Despite a higher risk of severe COVID-19 disease in individuals with HIV, the interactions between SARS-CoV-2 and HIV infections remain unclear. To delineate these interactions, multicentre Electronic Health Records (EHR) hold existing promise to provide full-spectrum and longitudinal clinical data, demographics and sociobehavioural data at individual level. Presently, a comprehensive EHR-based cohort for the HIV/SARS-CoV-2 coinfection has not been established; EHR integration and data mining methods tailored for studying the coinfection are urgently needed yet remain underdeveloped. METHODS AND ANALYSIS: The overarching goal of this exploratory/developmental study is to establish an EHR-based cohort for individuals with HIV/SARS-CoV-2 coinfection and perform large-scale EHR-based data mining to examine the interactions between HIV and SARS-CoV-2 infections and systematically identify and validate factors contributing to the severe clinical course of the coinfection. We will use a nationwide EHR database in the USA, namely, National COVID Cohort Collaborative (N3C). Ultimately, collected clinical evidence will be implemented and used to pilot test a clinical decision support prototype to assist providers in screening and referral of at-risk patients in real-world clinics. ETHICS AND DISSEMINATION: The study was approved by the institutional review boards at the University of South Carolina (Pro00121828) as non-human subject study. Study findings will be presented at academic conferences and published in peer-reviewed journals. This study will disseminate urgently needed clinical evidence for guiding clinical practice for individuals with the coinfection at Prisma Health, a healthcare system in collaboration.

A biomedical knowledge graph-based method for drug-drug interactions prediction through combining local and global features with deep neural networks.

Drug-drug interactions (DDIs) prediction is a challenging task in drug development and clinical application. Due to the extremely large complete set of all possible DDIs, computer-aided DDIs prediction methods are getting lots of attention in the pharmaceutical industry and academia. However, most existing computational methods only use single perspective information and few of them conduct the task based on the biomedical knowledge graph (BKG), which can provide more detailed and comprehensive drug lateral side information flow. To this end, a deep learning framework, namely DeepLGF, is proposed to fully exploit BKG fusing local-global information to improve the performance of DDIs prediction. More specifically, DeepLGF first obtains chemical local information on drug sequence semantics through a natural language processing algorithm. Then a model of BFGNN based on graph neural network is proposed to extract biological local information on drug through learning embedding vector from different biological functional spaces. The global feature information is extracted from the BKG by our knowledge graph embedding method. In DeepLGF, for fusing local-global features well, we designed four aggregating methods to explore the most suitable ones. Finally, the advanced fusing feature vectors are fed into deep neural network to train and predict. To evaluate the prediction performance of DeepLGF, we tested our method in three prediction tasks and compared it with state-of-the-art models. In addition, case studies of three cancer-related and COVID-19-related drugs further demonstrated DeepLGF's superior ability for potential DDIs prediction. The webserver of the DeepLGF predictor is freely available at http://120.77.11.78/DeepLGF/.

Roy Adaptation Model: Theory-Based Knowledge and Nursing Care With a Person Experiencing COVID-19.

Nursing theories shed light and guide nursing care through provision of care to persons based on the specialized knowledge base of the profession. Nurses utilizing Roy's adaptation model deliver holistic care by accounting for people, processes, and the environments. The aim of this article is to illustrate the value of utilizing the Roy adaptation model in the care of a patients by reviewing nursing care provided to a patient diagnosed with COVID-19.

Databases, Knowledgebases, and Software Tools for Virus Informatics.

Virus infection is a common social health issue. In the past decades, serious virus infectious events have caused great loss in people's life and the economics. The nature of rapid widespread and frequent variation increases the difficulty for precision viral prevention and treatment. In the era of big data and artificial intelligence (AI), advances in bioinformatics techniques bring unprecedented opportunities for virus informatics study, which contribute to the systems-level modeling of virus biology. In this chapter, data resources including virus-related databases and knowledgebases are introduced. Bioinformatics models and software tools for multiple sequence alignment, evolutionary analysis, and genome-wide research of viruses are summarized and emphasized. Translational applications of recently developed data-driven and AI-assisted methods to viral cases such as SARS-CoV-2, HBV/HCV, and influenza virus are discussed. Finally, the concept and significance of virus informatics are highlighted for both virus surveillance and health promotion.

Performance of a knowledge-based planning model for optimizing intensity-modulated radiotherapy plans for partial breast irradiation.

PURPOSE: To evaluate a knowledge-based (KB) planning model for RapidPlan, generated using a five-field intensity-modulated radiotherapy (IMRT) class solution beam strategy and rigorous dosimetric constraints for accelerated partial breast irradiation (APBI). MATERIALS AND METHODS: The RapidPlan model was configured using 64 APBI treatment plans and validated for 120 APBI patients who were not included in the training dataset. KB plan dosimetry was compared to clinical plan dosimetry, the clinical planning constraints, and the constraints used in phase III APBI trials. Dosimetric differences between clinical and KB plans were evaluated using paired two-tailed Wilcoxon signed-rank tests. RESULTS: KB planning was able to produce IMRT-based APBI plans in a single optimization without manual intervention that are comparable or better than the conventionally optimized, clinical plans. Comparing KB plans to clinical plans, differences in PTV, heart, contralateral breast, and ipsilateral lung dose-volume metrics were not clinically significant. The ipsilateral breast volume receiving at least 50% of the prescription dose was statistically and clinically significantly lower in the KB plans. CONCLUSION: KB planning for IMRT-based APBI provides equivalent or better dosimetry compared to conventional inverse planning. This model may be reliably applied in clinical practice and could be used to transfer planning expertise to ensure consistency in APBI plan quality.

Defining clinical outcome pathways.

Here, we propose a broad concept of 'Clinical Outcome Pathways' (COPs), which are defined as a series of key molecular and cellular events that underlie therapeutic effects of drug molecules. We formalize COPs as a chain of the following events: molecular initiating event (MIE) â†’ intermediate event(s) â†’ clinical outcome. We illustrate the concept with COP examples both for primary and alternative (i.e., drug repurposing) therapeutic applications. We also describe the elucidation of COPs for several drugs of interest using the publicly accessible Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways (ROBOKOP) biomedical knowledge graph-mining tool. We propose that broader use of COP uncovered with the help of biomedical knowledge graph mining will likely accelerate drug discovery and repurposing efforts.

The reactome pathway knowledgebase 2022.

The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied ('dark') proteins from analyzed datasets in the context of Reactome's manually curated pathways.

ICD-11: an international classification of diseases for the twenty-first century.

BACKGROUND: The International Classification of Diseases (ICD) has long been the main basis for comparability of statistics on causes of mortality and morbidity between places and over time. This paper provides an overview of the recently completed 11th revision of the ICD, focusing on the main innovations and their implications. MAIN TEXT: Changes in content reflect knowledge and perspectives on diseases and their causes that have emerged since ICD-10 was developed about 30 years ago. Changes in design and structure reflect the arrival of the networked digital era, for which ICD-11 has been prepared. ICD-11's information framework comprises a semantic knowledge base (the Foundation), a biomedical ontology linked to the Foundation and classifications derived from the Foundation. ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS) is the primary derived classification and the main successor to ICD-10. Innovations enabled by the new architecture include an online coding tool (replacing the index and providing additional functions), an application program interface to enable remote access to ICD-11 content and services, enhanced capability to capture and combine clinically relevant characteristics of cases and integrated support for multiple languages. CONCLUSIONS: ICD-11 was adopted by the World Health Assembly in May 2019. Transition to implementation is in progress. ICD-11 can be accessed at icd.who.int.

Evidence-Based Health Intelligence with Globally Localized Epidemic Knowledge Base: Merging Pathological Data, Socio-Environmental Data and Intervention Knowledge Data.

The increased prevalence and frequency of infectious diseases are alarming with respect to the disproportionate fatalities across different regions, socio-economic conditions, and demographic groups. Combining pathological data, socio-environmental data, and extracted knowledge from white papers, we proposed a Globally Localized Epidemic Knowledge base (GLEK) that can be utilized for efficient and optimal epidemic surveillance. GLEK merges social, environmental, pathological, and governmental intervention data to provide efficient advice for epidemic control and intervention. Heuristically utilizing multi-locus data sources, GLEK can identify the best tailored intervention.

Beyond the Chemotherapy Certificate: Building a Knowledge Base Virtually for Oncology Nursing Practice Across a Health System.

In a 51-hospital system serving seven states in the western United States, an organizational assessment in 2016 indicated critical staff shortages in one region for chemotherapy and immunotherapy-trained nurses. Leadership across the system was also concerned about nurse retention and turnover rates. Oncology nursing professional development practitioners designed and implemented a new multimodal oncology curriculum that utilizes a flipped classroom technique. Results indicate that first-year turnover rates were lower in nurses who participated. Healthcare systems are encouraged to invest in organizational infrastructure to implement nurse transition into practice programs to prepare, sustain, and stimulate specialization in oncology nursing.

Toward a Coronavirus Knowledge Graph.

This study builds a coronavirus knowledge graph (KG) by merging two information sources. The first source is Analytical Graph (AG), which integrates more than 20 different public datasets related to drug discovery. The second source is CORD-19, a collection of published scientific articles related to COVID-19. We combined both chemo genomic entities in AG with entities extracted from CORD-19 to expand knowledge in the COVID-19 domain. Before populating KG with those entities, we perform entity disambiguation on CORD-19 collections using Wikidata. Our newly built KG contains at least 21,700 genes, 2500 diseases, 94,000 phenotypes, and other biological entities (e.g., compound, species, and cell lines). We define 27 relationship types and use them to label each edge in our KG. This research presents two cases to evaluate the KG's usability: analyzing a subgraph (ego-centered network) from the angiotensin-converting enzyme (ACE) and revealing paths between biological entities (hydroxychloroquine and IL-6 receptor; chloroquine and STAT1). The ego-centered network captured information related to COVID-19. We also found significant COVID-19-related information in top-ranked paths with a depth of three based on our path evaluation.

VirusViz: comparative analysis and effective visualization of viral nucleotide and amino acid variants.

Variant visualization plays an important role in supporting the viral evolution analysis, extremely valuable during the COVID-19 pandemic. VirusViz is a web-based application for comparing variants of selected viral populations and their sub-populations; it is primarily focused on SARS-CoV-2 variants, although the tool also supports other viral species (SARS-CoV, MERS-CoV, Dengue, Ebola). As input, VirusViz imports results of queries extracting variants and metadata from the large database ViruSurf, which integrates information about most SARS-CoV-2 sequences publicly deposited worldwide. Moreover, VirusViz accepts sequences of new viral populations as multi-FASTA files plus corresponding metadata in CSV format; a bioinformatic pipeline builds a suitable input for VirusViz by extracting the nucleotide and amino acid variants. Pages of VirusViz provide metadata summarization, variant descriptions, and variant visualization with rich options for zooming, highlighting variants or regions of interest, and switching from nucleotides to amino acids; sequences can be grouped, groups can be comparatively analyzed. For SARS-CoV-2, we manually collect mutations with known or predicted levels of severity/virulence, as indicated in linked research articles; such critical mutations are reported when observed in sequences. The system includes light-weight project management for downloading, resuming, and merging data analysis sessions. VirusViz is freely available at http://gmql.eu/virusviz/.

A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization.

The SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community's massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made. In this paper, we present the COVID-19 PHARMACOME, a comprehensive drug-target-mechanism graph generated from a compilation of 10 separate disease maps and sources of experimental data focused on SARS-CoV-2/COVID-19 pathophysiology. By applying our systematic approach, we were able to predict the synergistic effect of specific drug pairs, such as Remdesivir and Thioguanosine or Nelfinavir and Raloxifene, on SARS-CoV-2 infection. Experimental validation of our results demonstrate that our graph can be used to not only explore the involved mechanistic pathways, but also to identify novel combinations of drug repurposing candidates.

Unknown Disease Outbreaks Detection: A Pilot Study on Feature-Based Knowledge Representation and Reasoning Model.

Background: The outbreak of COVID-19 in 2019 has rapidly swept the world, causing irreparable loss to human beings. The pandemic has shown that there is still a delay in the early response to disease outbreaks and needs a method for unknown disease outbreak detection. The study's objective is to establish a new medical knowledge representation and reasoning model, and use the model to explore the feasibility of unknown disease outbreak detection. Methods: The study defined abnormal values with diagnostic significances from clinical data as the Features, and defined the Features as the antecedents of inference rules to match with knowledge bases, achieved in detecting known or emerging infectious disease outbreaks. Meanwhile, the study built a syndromic surveillance base to capture the target cases' Features to improve the reliability and fault-tolerant ability of the system. Results: The study combined the method with Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and early COVID-19 outbreaks as empirical studies. The results showed that with suitable surveillance guidelines, the method proposed in this study was capable to detect outbreaks of SARS, MERS, and early COVID-19 pandemics. The quick matching accuracies of confirmed infection cases were 89.1, 26.3-98%, and 82%, and the syndromic surveillance base would capture the Features of the remaining cases to ensure the overall detection accuracies. Based on the early COVID-19 data in Wuhan, this study estimated that the median time of the early COVID-19 cases from illness onset to local authorities' responses could be reduced to 7.0-10.0 days. Conclusions: This study offers a new solution to transfer traditional medical knowledge into structured data and form diagnosis rules, enables the representation of doctors' logistic thinking and the knowledge transmission among different users. The results of empirical studies demonstrate that by constantly inputting medical knowledge into the system, the proposed method will be capable to detect unknown diseases from existing ones and perform an early response to the initial outbreaks.

4S-DT: Self-Supervised Super Sample Decomposition for Transfer Learning With Application to COVID-19 Detection.

Due to the high availability of large-scale annotated image datasets, knowledge transfer from pretrained models showed outstanding performance in medical image classification. However, building a robust image classification model for datasets with data irregularity or imbalanced classes can be a very challenging task, especially in the medical imaging domain. In this article, we propose a novel deep convolutional neural network, which we called self-supervised super sample decomposition for transfer learning (4S-DT) model. The 4S-DT encourages a coarse-to-fine transfer learning from large-scale image recognition tasks to a specific chest X-ray image classification task using a generic self-supervised sample decomposition approach. Our main contribution is a novel self-supervised learning mechanism guided by a super sample decomposition of unlabeled chest X-ray images. 4S-DT helps in improving the robustness of knowledge transformation via a downstream learning strategy with a class-decomposition (CD) layer to simplify the local structure of the data. The 4S-DT can deal with any irregularities in the image dataset by investigating its class boundaries using a downstream CD mechanism. We used 50000 unlabeled chest X-ray images to achieve our coarse-to-fine transfer learning with an application to COVID-19 detection, as an exemplar. The 4S-DT has achieved a high accuracy of 99.8% on the larger of the two datasets used in the experimental study and an accuracy of 97.54% on the smaller dataset, which was enriched by augmented images, out of which all real COVID-19 cases were detected.

An Emergent Network for the Diffusion of Innovations Among Local Health Departments at the Onset of the COVID-19 Pandemic.

INTRODUCTION: Communication networks among professionals can be pathways for accelerating the diffusion of innovations if some local health departments (LHDs) drive the spread of knowledge. Such a network could prove valuable during public health emergencies such as the novel coronavirus disease 2019 (COVID-19) pandemic. Our objective was to determine whether LHDs in the United States were tied together in an informal network to share information and advice about innovative community health practices, programs, and policies. METHODS: In January and February 2020, we conducted an online survey of 2,303 senior LHD leaders to ask several questions about their sources of advice. We asked respondents to rank up to 3 other LHDs whose practices informed their work on new public health programs, evidence-based practices, and policies intended to improve community health. We used a social network analysis program to assess answers. RESULTS: A total of 329 LHDs responded. An emergent network appeared to operate nationally among 740 LHDs. Eleven LHDs were repeatedly nominated by peers as sources of advice or examples (ie, opinion leaders), and 24 acted as relational bridges to hold these emergent networks together (ie, boundary spanners). Although 2 LHDs played both roles, most LHDs we surveyed performed neither of these roles. CONCLUSION: Opinion leading and boundary spanning health departments can be accessed to increase the likelihood of affecting the rate of interest in and adoption of innovations. Decision makers involved in disseminating new public health practices, programs, or policies may find our results useful both for emergencies and for practice-as-usual.

Ontological modeling and analysis of experimentally or clinically verified drugs against coronavirus infection.

Our systematic literature collection and annotation identified 106 chemical drugs and 31 antibodies effective against the infection of at least one human coronavirus (including SARS-CoV, SAR-CoV-2, and MERS-CoV) in vitro or in vivo in an experimental or clinical setting. A total of 163 drug protein targets were identified, and 125 biological processes involving the drug targets were significantly enriched based on a Gene Ontology (GO) enrichment analysis. The Coronavirus Infectious Disease Ontology (CIDO) was used as an ontological platform to represent the anti-coronaviral drugs, chemical compounds, drug targets, biological processes, viruses, and the relations among these entities. In addition to new term generation, CIDO also adopted various terms from existing ontologies and developed new relations and axioms to semantically represent our annotated knowledge. The CIDO knowledgebase was systematically analyzed for scientific insights. To support rational drug design, a "Host-coronavirus interaction (HCI) checkpoint cocktail" strategy was proposed to interrupt the important checkpoints in the dynamic HCI network, and ontologies would greatly support the design process with interoperable knowledge representation and reasoning.