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Background A quantitative trait locus (QTL) is a genomic region that correlates with a phenotype. Most of the experimental information about QTL mapping studies is described in tables of scientific publications. Traditional text mining techniques aim to extract information from unstructured text rather than from tables. We present QTLTableMiner ++ (QTM), a table mining tool that extracts and semantically annotates QTL information buried in (heterogeneous) tables of plant science literature. QTM is a command line tool written in the Java programming language. This tool takes scientific articles from the Europe PMC repository as input, extracts QTL tables using keyword matching and ontology-based concept identification. The tables are further normalized using rules derived from table properties such as captions, column headers and table footers. Furthermore, table columns are classified into three categories namely column descriptors, properties and values based on column headers and data types of cell entries. Abbreviations found in the tables are expanded using the Schwartz and Hearst algorithm. Finally, the content of QTL tables is semantically enriched with domain-specific ontologies (e.g. Crop Ontology, Plant Ontology and Trait Ontology) using the Apache Solr search platform and the results are stored in a relational database and a text file. Results The performance of the QTM tool was assessed by precision and recall based on the information retrieved from two manually annotated corpora of open access articles, i.e. QTL mapping studies in tomato ( Solanum lycopersicum ) and in potato ( S. tuberosum ). In summary, QTM detected QTL statements in tomato with 74.53% precision and 92.56% recall and in potato with 82.82% precision and 98.94% recall. Conclusion QTM is a unique tool that aids in providing QTL information in machine-readable and semantically interoperable formats.

Electronic health records (EHRs) consist of both structured data (eg, diagnostic codes) and unstructured data (eg, clinical notes). It is commonly believed that unstructured clinical narratives provide more comprehensive information. However, this assumption lacks large-scale validation and direct validation methods. This study aims to quantitatively compare the information in structured and unstructured EHR data and directly validate whether unstructured data offers more extensive information across a patient population. We analyzed both structured and unstructured data from patient records and visits in a large Dutch primary care EHR database between January 2021 and January 2024. Clinical concepts were identified from free-text notes using an extraction framework tailored for Dutch and compared with concepts from structured data. Concept embeddings were generated to measure semantic similarity between structured and extracted concepts through cosine similarity. A similarity threshold was systematically determined via annotated matches and minimized weighted Gini impurity. We then quantified the concept overlap between structured and unstructured data across various concept domains and patient populations. In a population of 1.8 million patients, only 13% of extracted concepts from patient records and 7% from individual visits had similar structured counterparts. Conversely, 42% of structured concepts in records and 25% in visits had similar matches in unstructured data. Condition concepts had the highest overlap, followed by measurements and drug concepts. Subpopulation visits, such as those with chronic conditions or psychological disorders, showed different proportions of data overlap, indicating varied reliance on structured versus unstructured data across clinical contexts. Our study demonstrates the feasibility of quantifying the information difference between structured and unstructured data, showing that the unstructured data provides important additional information in the studied database and populations. The annotated concept matches are made publicly available for the clinical natural language processing community. Despite some limitations, our proposed methodology proves versatile, and its application can lead to more robust and insightful observational clinical research.

Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) that play important roles in the genetic heritability of traits and diseases. With most of these SNPs located on the non-coding part of the genome, it is currently assumed that these SNPs influence the expression of nearby genes on the genome. However, identifying which genes are targeted by these disease-associated SNPs remains challenging. In the past, protein knowledge graphs have often been used to identify genes that are associated with disease, also referred to as “disease genes”. Here, we explore whether protein knowledge graphs can be used to identify genes that are targeted by disease-associated non-coding SNPs by testing and comparing the performance of six existing methods for a protein knowledge graph, four of which were developed for disease gene identification. We compare our performance against two baselines: (1) an existing state-of-the-art method that is based on guilt-by-association, and (2) the leading assumption that SNPs target the nearest gene on the genome. We test these methods with four reference sets, three of which were obtained by different means. Furthermore, we combine methods to investigate whether their combination improves performance. We find that protein knowledge graphs that include predicate information perform comparable to the current state of the art, achieving an area under the receiver operating characteristic curve (AUC) of 79.6% on average across all four reference sets. Protein knowledge graphs that lack predicate information perform comparable to our other baseline (genetic distance) which achieved an AUC of 75.7% across all four reference sets. Combining multiple methods improved performance to 84.9% AUC. We conclude that methods for a protein knowledge graph can be used to identify which genes are targeted by disease-associated non-coding SNPs.

Compounds that are candidates for drug repurposing can be ranked by leveraging knowledge available in the biomedical literature and databases. This knowledge, spread across a variety of sources, can be integrated within a knowledge graph, which thereby comprehensively describes known relationships between biomedical concepts, such as drugs, diseases, genes, etc. Our work uses the semantic information between drug and disease concepts as features, which are extracted from an existing knowledge graph that integrates 200 different biological knowledge sources. RepoDB, a standard drug repurposing database which describes drug-disease combinations that were approved or that failed in clinical trials, is used to train a random forest classifier. The 10-times repeated 10-fold cross-validation performance of the classifier achieves a mean area under the receiver operating characteristic curve (AUC) of 92.2%. We apply the classifier to prioritize 21 preclinical drug repurposing candidates that have been suggested for Autosomal Dominant Polycystic Kidney Disease (ADPKD). Mozavaptan, a vasopressin V2 receptor antagonist is predicted to be the drug most likely to be approved after a clinical trial, and belongs to the same drug class as tolvaptan, the only treatment for ADPKD that is currently approved. We conclude that semantic properties of concepts in a knowledge graph can be exploited to prioritize drug repurposing candidates for testing in clinical trials.

Background The eTRANSAFE project developed tools that support translational research. One of the challenges in this project was to combine preclinical and clinical data, which are coded with different terminologies and granularities, and are expressed as single pre-coordinated, clinical concepts and as combinations of preclinical concepts from different terminologies. This study develops and evaluates the Rosetta Stone approach, which maps combinations of preclinical concepts to clinical, pre-coordinated concepts, allowing for different levels of exactness of mappings. Methods Concepts from preclinical and clinical terminologies used in eTRANSAFE have been mapped to the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). SNOMED CT acts as an intermediary terminology that provides the semantics to bridge between pre-coordinated clinical concepts and combinations of preclinical concepts with different levels of granularity. The mappings from clinical terminologies to SNOMED CT were taken from existing resources, while mappings from the preclinical terminologies to SNOMED CT were manually created. A coordination template defines the relation types that can be explored for a mapping and assigns a penalty score that reflects the inexactness of the mapping. A subset of 60 pre-coordinated concepts was mapped both with the Rosetta Stone semantic approach and with a lexical term matching approach. Both results were manually evaluated. Results A total of 34,308 concepts from preclinical terminologies (Histopathology terminology, Standard for Exchange of Nonclinical Data (SEND) code lists, Mouse Adult Gross Anatomy Ontology) and a clinical terminology (MedDRA) were mapped to SNOMED CT as the intermediary bridging terminology. A terminology service has been developed that returns dynamically the exact and inexact mappings between preclinical and clinical concepts. On the evaluation set, the precision of the mappings from the terminology service was high (95%), much higher than for lexical term matching (22%). Conclusion The Rosetta Stone approach uses a semantically rich intermediate terminology to map between pre-coordinated clinical concepts and a combination of preclinical concepts with different levels of exactness. The possibility to generate not only exact but also inexact mappings allows to relate larger amounts of preclinical and clinical data, which can be helpful in translational use cases.

Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL-4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab. Methods: Spontaneous reports were used from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities ® (MedDRA ® ). Safety signal strength was assessed by the Reporting Odds Ratio (ROR). Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24–63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4–29.3). Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation.

Data in the life sciences are extremely diverse and are stored in a broad spectrum of repositories ranging from those designed for particular data types (such as KEGG for pathway data or UniProt for protein data) to those that are general-purpose (such as FigShare, Zenodo, Dataverse or EUDAT). These data have widely different levels of sensitivity and security considerations. For example, clinical observations about genetic mutations in patients are highly sensitive, while observations of species diversity are generally not. The lack of uniformity in data models from one repository to another, and in the richness and availability of metadata descriptions, makes integration and analysis of these data a manual, time-consuming task with no scalability. Here we explore a set of resource-oriented Web design patterns for data discovery, accessibility, transformation, and integration that can be implemented by any general- or special-purpose repository as a means to assist users in finding and reusing their data holdings. We show that by using off-the-shelf technologies, interoperability can be achieved atthe level of an individual spreadsheet cell. We note that the behaviours of this architecture compare favourably to the desiderata defined by the FAIR Data Principles, and can therefore represent an exemplar implementation of those principles. The proposed interoperability design patterns may be used to improve discovery and integration of both new and legacy data, maximizing the utility of all scholarly outputs.

Background To train chunkers in recognizing noun phrases and verb phrases in biomedical text, an annotated corpus is required. The creation of gold standard corpora (GSCs), however, is expensive and time-consuming. GSCs therefore tend to be small and to focus on specific subdomains, which limits their usefulness. We investigated the use of a silver standard corpus (SSC) that is automatically generated by combining the outputs of multiple chunking systems. We explored two use scenarios: one in which chunkers are trained on an SSC in a new domain for which a GSC is not available, and one in which chunkers are trained on an available, although small GSC but supplemented with an SSC. Results We have tested the two scenarios using three chunkers, Lingpipe, OpenNLP, and Yamcha, and two different corpora, GENIA and PennBioIE. For the first scenario, we showed that the systems trained for noun-phrase recognition on the SSC in one domain performed 2.7-3.1 percentage points better in terms of F-score than the systems trained on the GSC in another domain, and only 0.2-0.8 percentage points less than when they were trained on a GSC in the same domain as the SSC. When the outputs of the chunkers were combined, the combined system showed little improvement when using the SSC. For the second scenario, the systems trained on a GSC supplemented with an SSC performed considerably better than systems that were trained on the GSC alone, especially when the GSC was small. For example, training the chunkers on a GSC consisting of only 10 abstracts but supplemented with an SSC yielded similar performance as training them on a GSC of 100-250 abstracts. The combined system even performed better than any of the individual chunkers trained on a GSC of 500 abstracts. Conclusions We conclude that an SSC can be a viable alternative for or a supplement to a GSC when training chunkers in a biomedical domain. A combined system only shows improvement if the SSC is used to supplement a GSC. Whether the approach is applicable to other systems in a natural-language processing pipeline has to be further investigated.

Background Vaccine information in European electronic health record (EHR) databases is represented using various clinical and database-specific coding systems and drug vocabularies. The lack of harmonization constitutes a challenge in reusing EHR data in collaborative benefit-risk studies about vaccines. Methods We designed an ontology of the properties that are commonly used in vaccine descriptions, called Ontology of Vaccine Descriptions (VaccO), with a dictionary for the analysis of multilingual vaccine descriptions. We implemented five algorithms for the alignment of vaccine coding systems, i.e., the identification of corresponding codes from different coding ystems, based on an analysis of the code descriptors. The algorithms were evaluated by comparing their results with manually created alignments in two reference sets including clinical and database-specific coding systems with multilingual code descriptors. Results The best-performing algorithm represented code descriptors as logical statements about entities in the VaccO ontology and used an ontology reasoner to infer common properties and identify corresponding vaccine codes. The evaluation demonstrated excellent performance of the approach (F-scores 0.91 and 0.96). Conclusion The VaccO ontology allows the identification, representation, and comparison of heterogeneous descriptions of vaccines. The automatic alignment of vaccine coding systems can accelerate the readiness of EHR databases in collaborative vaccine studies.

Background Biomedical knowledge graphs have become important tools to computationally analyse the comprehensive body of biomedical knowledge. They represent knowledge as subject-predicate-object triples, in which the predicate indicates the relationship between subject and object. A triple can also contain provenance information, which consists of references to the sources of the triple (e.g. scientific publications or database entries). Knowledge graphs have been used to classify drug-disease pairs for drug efficacy screening, but existing computational methods have often ignored predicate and provenance information. Using this information, we aimed to develop a supervised machine learning classifier and determine the added value of predicate and provenance information for drug efficacy screening. To ensure the biological plausibility of our method we performed our research on the protein level, where drugs are represented by their drug target proteins, and diseases by their disease proteins. Results Using random forests with repeated 10-fold cross-validation, our method achieved an area under the ROC curve (AUC) of 78.1% and 74.3% for two reference sets. We benchmarked against a state-of-the-art knowledge-graph technique that does not use predicate and provenance information, obtaining AUCs of 65.6% and 64.6%, respectively. Classifiers that only used predicate information performed superior to classifiers that only used provenance information, but using both performed best. Conclusion We conclude that both predicate and provenance information provide added value for drug efficacy screening.