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Abstract Background Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. ClinicalTrials.gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance. Results In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, the Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate’s accuracy and 90.0% on top 10 candidate’s accuracy. Conclusion This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.

Abstract Background The Vaccine Ontology (VO) is a biomedical ontology that standardizes vaccine annotation. Errors in VO will affect a multitude of applications that it is being used in. Quality assurance of VO is imperative to ensure that it provides accurate domain knowledge to these downstream tasks. Manual review to identify and fix quality issues (such as missing hierarchical is-a relations) is challenging given the complexity of the ontology. Automated approaches are highly desirable to facilitate the quality assurance of VO. Methods We developed an automated lexical approach that identifies potentially missing is-a relations in VO. First, we construct two types of VO concept-pairs: (1) linked; and (2) unlinked. Each concept-pair further derives an Acquired Term Pair (ATP) based on their lexical features. If the same ATP is obtained by a linked concept-pair and an unlinked concept-pair, this is considered to indicate a potentially missing is-a relation between the unlinked pair of concepts. Results Applying this approach on the 1.1.192 version of VO, we were able to identify 232 potentially missing is-a relations. A manual review by a VO domain expert on a random sample of 70 potentially missing is-a relations revealed that 65 of the cases were valid missing is-a relations in VO (a precision of 92.86%). Conclusions The results indicate that our approach is highly effective in identifying missing is-a relation in VO.

Abstract Background In this paper, we discuss the design and development of a formal ontology to describe misinformation about vaccines. Vaccine misinformation is one of the drivers leading to vaccine hesitancy in patients. While there are various levels of vaccine hesitancy to combat and specific interventions to address those levels, it is important to have tools that help researchers understand this problem. With an ontology, not only can we collect and analyze varied misunderstandings about vaccines, but we can also develop tools that can provide informatics solutions. Results We developed the Vaccine Misinformation Ontology (VAXMO) that extends the Misinformation Ontology and links to the nanopublication Resource Description Framework (RDF) model for false assertions of vaccines. Preliminary assessment using semiotic evaluation metrics indicated adequate quality for our ontology. We outlined and demonstrated proposed uses of the ontology to detect and understand anti-vaccine information. Conclusion We surmised that VAXMO and its proposed use cases can support tools and technology that can pave the way for vaccine misinformation detection and analysis. Using an ontology, we can formally structure knowledge for machines and software to better understand the vaccine misinformation domain.

Abstract Background Detailed Clinical Models (DCMs) have been regarded as the basis for retaining computable meaning when data are exchanged between heterogeneous computer systems. To better support clinical cancer data capturing and reporting, there is an emerging need to develop informatics solutions for standards-based clinical models in cancer study domains. The objective of the study is to develop and evaluate a cancer genome study metadata management system that serves as a key infrastructure in supporting clinical information modeling in cancer genome study domains. Methods We leveraged a Semantic Web-based metadata repository enhanced with both ISO11179 metadata standard and Clinical Information Modeling Initiative (CIMI) Reference Model. We used the common data elements (CDEs) defined in The Cancer Genome Atlas (TCGA) data dictionary, and extracted the metadata of the CDEs using the NCI Cancer Data Standards Repository (caDSR) CDE dataset rendered in the Resource Description Framework (RDF). The ITEM/ITEM_GROUP pattern defined in the latest CIMI Reference Model is used to represent reusable model elements (mini-Archetypes). Results We produced a metadata repository with 38 clinical cancer genome study domains, comprising a rich collection of mini-Archetype pattern instances. We performed a case study of the domain “clinical pharmaceutical” in the TCGA data dictionary and demonstrated enriched data elements in the metadata repository are very useful in support of building detailed clinical models. Conclusion Our informatics approach leveraging Semantic Web technologies provides an effective way to build a CIMI-compliant metadata repository that would facilitate the detailed clinical modeling to support use cases beyond TCGA in clinical cancer study domains.

Abstract Background Research for ontology evaluation is scarce. If biomedical ontological datasets and knowledgebases are to be widely used, there needs to be quality control and evaluation for the content and structure of the ontology. This paper introduces how to effectively utilize a semiotic-inspired approach to ontology evaluation, specifically towards drug-related ontologies hosted on the National Center for Biomedical Ontology BioPortal. Results Using the semiotic-based evaluation framework for drug-based ontologies, we adjusted the quality metrics based on the semiotic features of drug ontologies. Then, we compared the quality scores before and after tailoring. The scores revealed a more precise measurement and a closer distribution compared to the before-tailoring. Conclusion The results of this study reveal that a tailored semiotic evaluation produced a more meaningful and accurate assessment of drug-based ontologies, lending to the possible usefulness of semiotics in ontology evaluation.

Background: Detailed Clinical Models (DCMs) have been regarded as the basis for retaining computable meaning when data are exchanged between heterogeneous computer systems. To better support clinical cancer data capturing and reporting, there is an emerging need to develop informatics solutions for standards-based clinical models in cancer study domains. The objective of the study is to develop and evaluate a cancer genome study metadata management system that serves as a key infrastructure in supporting clinical information modeling in cancer genome study domains. Methods: We leveraged a Semantic Web-based metadata repository enhanced with both ISO11179 metadata standard and Clinical Information Modeling Initiative (CIMI) Reference Model. We used the common data elements (CDEs) defined in The Cancer Genome Atlas (TCGA) data dictionary, and extracted the metadata of the CDEs using the NCI Cancer Data Standards Repository (caDSR) CDE dataset rendered in the Resource Description Framework (RDF). The ITEM/ITEM_GROUP pattern defined in the latest CIMI Reference Model is used to represent reusable model elements (mini-Archetypes). Results: We produced a metadata repository with 38 clinical cancer genome study domains, comprising a rich collection of mini-Archetype pattern instances. We performed a case study of the domain "clinical pharmaceutical" in the TCGA data dictionary and demonstrated enriched data elements in the metadata repository are very useful in support of building detailed clinical models. Conclusion: Our informatics approach leveraging Semantic Web technologies provides an effective way to build a CIMI-compliant metadata repository that would facilitate the detailed clinical modeling to support use cases beyond TCGA in clinical cancer study domains. [ABSTRACT FROM AUTHOR]

Background: Research for ontology evaluation is scarce. If biomedical ontological datasets and knowledgebases are to be widely used, there needs to be quality control and evaluation for the content and structure of the ontology. This paper introduces how to effectively utilize a semiotic-inspired approach to ontology evaluation, specifically towards drug-related ontologies hosted on the National Center for Biomedical Ontology BioPortal. Results: Using the semiotic-based evaluation framework for drug-based ontologies, we adjusted the quality metrics based on the semiotic features of drug ontologies. Then, we compared the quality scores before and after tailoring. The scores revealed a more precise measurement and a closer distribution compared to the before-tailoring. Conclusion: The results of this study reveal that a tailored semiotic evaluation produced a more meaningful and accurate assessment of drug-based ontologies, lending to the possible usefulness of semiotics in ontology evaluation. [ABSTRACT FROM AUTHOR]

Background: Analysing public opinions on HPV vaccines on social media using machine learning based approaches will help us understand the reasons behind the low vaccine coverage and come up with corresponding strategies to improve vaccine uptake. Objective: To propose a machine learning system that is able to extract comprehensive public sentiment on HPV vaccines on Twitter with satisfying performance. Method: We collected and manually annotated 6,000 HPV vaccines related tweets as a gold standard. SVM model was chosen and a hierarchical classification method was proposed and evaluated. Additional feature sets evaluation and model parameters optimization was done to maximize the machine learning model performance. Results: A hierarchical classification scheme that contains 10 categories was built to access public opinions toward HPV vaccines comprehensively. A 6,000 annotated tweets gold corpus with Kappa annotation agreement at 0.851 was created and made public available. The hierarchical classification model with optimized feature sets and model parameters has increased the micro-averaging and macro-averaging F score from 0.6732 and 0.3967 to 0.7442 and 0.5883 respectively, compared with baseline model. Conclusions: Our work provides a systematical way to improve the machine learning model performance on the highly unbalanced HPV vaccines related tweets corpus. Our system can be further applied on a large tweets corpus to extract large-scale public opinion towards HPV vaccines. [ABSTRACT FROM AUTHOR]

Background: Trivalent Influenza Virus Vaccine (FLU3) is a traditional flu vaccine to protect people against three different flu viruses, including influenza A H1N1 virus, an influenza A H3N2 virus and one B virus. Methods: We searched Vaccine Adverse Event Reporting System (VAERS) for US reports after FLU3 vaccination in the year of 2011. We conducted descriptive analyses on symptoms from serious reports (i.e., death, life-threatening illness, hospitalization, prolonged hospitalization, or permanent disability). We then further grouped these symptoms to the System Organ Classes (SOC) based on the MedDRA Terminology using NCBO Web Services. We fitted zero-truncated Poisson regression models to estimate the average number of symptoms per subject and compared it across different age groups and between genders. In addition, we compared the risk of occurrence for an SOC across different age groups and between genders by using logistic regression models. Finally, we constructed the pairwise correlation matrix of the SOCs by calculating Spearman's rank correlation coefficients. Results: We identified 638 unique serious FLU3 reports from year 2011. There are 1410 unique symptoms from these reports. Descriptive statistics shows that the most common symptom and symptom pair are Pyrexia and Guillain-Barre syndrome - Hypoesthesia respectively. The estimated average number of symptoms per subject in the study cohort is 8.74 (95% CI 6.76, 10.73). There are statistically significant differences in number of symptoms among four age groups and between genders. Age category and gender are significantly associated with several individual SOCs. Pairwise correlation matrix shows that "Endocrine disorders" and "Neoplasms benign, malignant and unspecified (incl cysts and polyps)" are strongly correlated. Conclusions: This paper reports a novel method that combining statistical analyses with terminology grouping using VAERS data. The analyses revealed differences of reactions among different age groups and between genders and correlation on both symptoms and System Organ Class level independently. The results may lead to additional studies to uncover factors contributing to the individual differences in susceptibility to influenza infection. This method can also be applied to other vaccine types and conduct similar analysis. [ABSTRACT FROM AUTHOR]

Background: Information about drug-drug interactions (DDIs) is crucial for computational applications such as pharmacovigilance and drug repurposing. However, existing sources of DDIs have the problems of low coverage, low accuracy and low agreement. One common type of DDIs is related to the mechanism of drug metabolism: a DDI relation may be caused by different interactions (e.g., substrate, inhibit) between drugs and enzymes in the drug metabolism process. Thus, information from drug enzyme interactions (DEIs) serves as important supportive evidence for DDIs. Further, potential DDIs present implicitly could be detected by inference and reasoning based on DEIs. Methods: In this article, we propose a hybrid approach to combining machine learning algorithm with trigger words and syntactic patterns, for DEI relation extraction from biomedical literature. The extracted DEI relations are used for reasoning to infer potential DDI relations, based on a defined drug-enzyme ontology incorporating biological knowledge. Results: Evaluation results demonstrate that the performance of DEI relation extraction is promising, with an F-measure of 84.97 % on the in vivo dataset and 65.58 % on the in vitro dataset. Further, the inferred DDIs achieved a precision of 83.19 % on the in vivo dataset and 70.94 % on the in vitro dataset, respectively. A further examination showed that the overlaps between our inferred DDIs and those present in DrugBank were 42.02 % on the in vivo dataset and 19.23 % on the in vitro dataset, respectively. Conclusions: This paper proposed an effective approach to extract DEI relations from biomedical literature. Potential DDIs not present in existing knowledge bases were then inferred based on the extracted DEIs, demonstrating the capability of the proposed approach to detect DDIs with scientific evidence for pharmacovigilance and drug repurposing applications. [ABSTRACT FROM AUTHOR]

Background: Vaccines are one of the most important public health successes in last century. Besides effectiveness in reducing the morbidity and mortality from many infectious diseases, a successful vaccine program also requires a rigorous assessment on their safety. Due to the limitations of adverse event (AE) data from clinical trials and post-approval surveillance systems, novel computational approaches are needed to organize, visualize, and analyze such high-dimensional complex data. Results: In this paper, we proposed a network-based approach to investigate the vaccine-AE association network from the Vaccine AE Reporting System (VAERS) data. Statistical summary was calculated using the VAERS raw data and represented in the Resource Description Framework (RDF). The RDF graph was leveraged for network analysis. Specifically, we compared network properties of (1) vaccine - adverse event association network based on reports collected over a 23 year period as well as each year; and (2) sex-specific vaccine-adverse event association network. We observed that (1) network diameter and average path length don't change dramatically over a 23-year period, while the average node degree of these networks changes due to the different number of reports during different periods of time; (2) vaccine - adverse event associations derived from different sexes show sex-associated patterns in sex-specific vaccine-AE association networks. Conclusions: We have developed a network-based approach to investigate the vaccine-AE association network from the VAERS data. To our knowledge, this is the first time that a network-based approach was used to identify sex-specific association patterns in a spontaneous reporting system database. Due to unique limitations of such passive surveillance systems, our proposed network-based approaches have the potential to summarize and analyze the associations in passive surveillance systems by (1) identifying nodes of importance, irrespective of whether they are disproportionally reported; (2) providing guidance on sex-specific recommendations in personalized vaccinology. [ABSTRACT FROM AUTHOR]

Objective: To construct a comprehensive vaccine information ontology that can support personal health information applications using patient-consumer lexicon, and lead to outcomes that can improve patient education. Methods: The authors composed the Vaccine Information Statement Ontology (VISO) using the web ontology language (OWL). We started with 6 Vaccine Information Statement (VIS) documents collected from the Centers for Disease Control and Prevention (CDC) website. Important and relevant selections from the documents were recorded, and knowledge triples were derived. Based on the collection of knowledge triples, the meta-level formalization of the vaccine information domain was developed. Relevant instances and their relationships were created to represent vaccine domain knowledge. Results: The initial iteration of the VISO was realized, based on the 6 Vaccine Information Statements and coded into OWL2 with Protégé. The ontology consisted of 132 concepts (classes and subclasses) with 33 types of relationships between the concepts. The total number of instances from classes totaled at 460, along with 429 knowledge triples in total. Semiotic-based metric scoring was applied to evaluate quality of the ontology. [ABSTRACT FROM AUTHOR]

In this paper, we show how we have applied the Clinical Narrative Temporal Relation Ontology (CNTRO) and its associated temporal reasoning system (the CNTRO Timeline Library) to trend temporal information within medical device adverse event report narratives. 238 narratives documenting occurrences of late stent thrombosis adverse events from the Food and Drug Administration's (FDA) Manufacturing and User Facility Device Experience (MAUDE) database were annotated and evaluated using the CNTRO Timeline Library to identify, order, and calculate the duration of temporal events. The CNTRO Timeline Library had a 95% accuracy in correctly ordering events within the 238 narratives. 41 narratives included an event in which the duration was documented, and the CNTRO Timeline Library had an 80% accuracy in correctly determining these durations. 77 narratives included documentation of a duration between events, and the CNTRO Timeline Library had a 76% accuracy in determining these durations. This paper also includes an example of how this temporal output from the CNTRO ontology can be used to verify recommendations for length of drug administration, and proposes that these same tools could be applied to other medical device adverse event narratives in order to identify currently unknown temporal trends. [ABSTRACT FROM AUTHOR]

The 2013 "Vaccine and Drug Ontology Studies" (VDOS 2013) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have contributed to dramatic improvements in public health worldwide. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs – extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, as well as developing new models such as Vaccine Ontology. The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The six full-length papers included in this thematic issue focuses on three main areas: (i) ontology development and representation, (ii) ontology mapping, maintaining and auditing, and (iii) ontology applications. [ABSTRACT FROM AUTHOR]

Background Ontologies are useful in many branches of biomedical research. For instance, in the vaccine domain, the community-based Vaccine Ontology (VO) has been widely used to promote vaccine data standardization, integration, and computer-assisted reasoning. However, a major challenge in the VO has been to construct ontologies of vaccine functions, given incomplete vaccine knowledge and inconsistencies in how this knowledge is manually curated. Results In this study, we show that network-based analysis of vaccine-related networks can identify underlying structural information consistent with that captured by the VO, and commonalities in the vaccine adverse events for vaccines and for diseases to produce new hypotheses about pathomechanisms involving the vaccine and the disease status. First, a vaccine-vaccine network was inferred by applying a bipartite network projection strategy to the vaccine-disease network extracted from the Semantic MEDLINE database. In total, 76 vaccines and 573 relationships were identified to construct the vaccine network. The shortest paths between all pairs of vaccines were calculated within the vaccine network. The correlation between the shortest paths of vaccine pairs and their semantic similarities in the VO was then investigated. Second, a vaccine-gene network was also constructed. In this network, 4 genes were identified as hubs interacting with at least 3 vaccines, and 4 vaccines were identified as hubs associated with at least 3 genes. These findings correlate with existing knowledge and provide new hypotheses in the fundamental interaction mechanisms involving vaccines, diseases, and genes. Conclusions In this study, we demonstrated that a combinatorial analysis using a literature knowledgebase, semantic technology, and ontology is able to reveal important unidentified knowledge critical to biomedical research and public health and to generate testable hypotheses for future experimental verification. As the associations from Semantic MEDLINE remain incomplete, we expect to extend this work by (1) integrating additional association databases to complement Semantic MEDLINE knowledge, (2) extending the neighbor genes of vaccineassociated genes, and (3) assigning confidence weights to different types of associations or associations from different sources. [ABSTRACT FROM AUTHOR]

Background: The U.S. FDA/CDC Vaccine Adverse Event Reporting System (VAERS) provides a valuable data source for post-vaccination adverse event analyses. The structured data in the system has been widely used, but the information in the write-up narratives is rarely included in these kinds of analyses. In fact, the unstructured nature of the narratives makes the data embedded in them difficult to be used for any further studies. Results: We developed an ontology-based approach to represent the data in the narratives in a "machine-understandable" way, so that it can be easily queried and further analyzed. Our focus is the time aspect in the data for time trending analysis. The Time Event Ontology (TEO), Ontology of Adverse Events (OAE), and Vaccine Ontology (VO) are leveraged for the semantic representation of this purpose. A VAERS case report is presented as a use case for the ontological representations. The advantages of using our ontology-based Semantic web representation and data analysis are emphasized. Conclusions: We believe that representing both the structured data and the data from write-up narratives in an integrated, unified, and "machine-understandable" way can improve research for vaccine safety analyses, causality assessments, and retrospective studies. [ABSTRACT FROM AUTHOR]

The "Vaccine and Drug Ontology Studies" (VDOS) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have been critical to prevent and treat human and animal diseases. Work in both (drugs and vaccines) areas is closely related - from preclinical research and development to manufacturing, clinical trials, government approval and regulation, and post-licensure usage surveillance and monitoring. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs - extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, developing new models such as the Vaccine Ontology (VO) and Ontology of Adverse Events (OAE), vernacular medical terminologies such as the Consumer Health Vocabulary (CHV). The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The five full-length papers included in this 2014 thematic issue focus on two main themes: (i) General vaccine/drug-related ontology development and exploration, and (ii) Interaction and network-related ontology studies. [ABSTRACT FROM AUTHOR]