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Objective: Drug repurposing accelerates therapeutic development by finding new indications for approved drugs. However, accounting for individual patient differences is challenging. This study introduces a Precision Drug Repurposing (PDR) framework at single-patient resolution, integrating individual-level data with a foundational biomedical knowledge graph to enable personalized drug discovery., Methods: We developed a framework integrating patient-specific data from the UK Biobank (Polygenic Risk Scores, biomarker expressions, and medical history) with a comprehensive biomedical knowledge graph (61,146 entities, 1,246,726 relations). Using Alzheimer's Disease as a case study, we compared three diverse patient-specific models with a foundational model through standard link prediction metrics. We evaluated top predicted candidate drugs using patient medication history and literature review., Results: Our framework maintained the robust prediction capabilities of the foundational model. The integration of patient data, particularly Polygenic Risk Scores (PRS), significantly influenced drug prioritization (Cohen's d = 1.05 for scoring differences). Ablation studies demonstrated PRS's crucial role, with effect size decreasing to 0.77 upon removal. Each patient model identified novel drug candidates that were missed by the foundational model but showed therapeutic relevance when evaluated using patient's own medication history. These candidates were further supported by aligned literature evidence with the patient-level genetic risk profiles based on PRS., Conclusion: This exploratory study demonstrates a promising approach to precision drug repurposing by integrating patient-specific data with a foundational knowledge graph., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Background: Knowledge graphs (KGs) remain an underutilized tool in the field of psychiatric research. In the broader biomedical field KGs are already a significant tool mainly used as knowledge database or for novel relation detection between biomedical entities. This review aims to outline how KGs would further research in the field of psychiatry in the age of Artificial Intelligence (AI) and Large Language Models (LLMs)., Methods: We conducted a thorough literature review across a spectrum of scientific fields ranging from computer science and knowledge engineering to bioinformatics. The literature reviewed was taken from PubMed, Semantic Scholar and Google Scholar searches including terms such as "Psychiatric Knowledge Graphs", "Biomedical Knowledge Graphs", "Knowledge Graph Machine Learning Applications", "Knowledge Graph Applications for Biomedical Sciences". The resulting publications were then assessed and accumulated in this review regarding their possible relevance to future psychiatric applications., Results: A multitude of papers and applications of KGs in associated research fields that are yet to be utilized in psychiatric research was found and outlined in this review. We create a thorough recommendation for other computational researchers regarding use-cases of these KG applications in psychiatry., Conclusion: This review illustrates use-cases of KG-based research applications in biomedicine and beyond that may aid in elucidating the complex biology of psychiatric illness and open new routes for developing innovative interventions. We conclude that there is a wealth of opportunities for KG utilization in psychiatric research across a variety of application areas including biomarker discovery, patient stratification and personalized medicine approaches., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.) more...

Knowledge graphs have been a useful tool for many biomedical applications because of their effective representation of biological concepts. Plentiful evidence exists linking the gut microbiome to disease in a correlative context, but uncovering the mechanistic explanation for those associations remains a challenge. Here we demonstrate the potential of knowledge graphs to hypothesize plausible mechanistic accounts of host-microbe interactions in disease. We have constructed a knowledge graph of linked microbes, genes and metabolites called MGMLink, and, using a shortest path or template-based search through the graph and a novel path-prioritization methodology based on the structure of the knowledge graph, we show that this knowledge supports inference of mechanistic hypotheses that explain observed relationships between microbes and disease phenotypes. We discuss specific applications of this methodology in inflammatory bowel disease and Parkinson's disease. This approach enables mechanistic hypotheses surrounding the complex interactions between gut microbes and disease to be generated in a scalable and comprehensive manner., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).) more...

Background: Despite the insights that metabolite analysis can provide into the onset, development, and progression of diseases-thus offering new concepts and methodologies for prevention, diagnosis, and treatment-traditional wet lab experiments are often time-consuming and labor-intensive. Consequently, this study aimed to develop a machine learning model named COM-RAN, which is based on a knowledge graph and random forest algorithm, to identify potential associations between metabolites and diseases., Methods: Firstly, we integrated the known associations between diseases and metabolites. Secondly, we provided a synthesis of the extant data regarding diseases and metabolites, accompanied by supplementary information pertinent to these entities. Thirdly, knowledge graph-based embedded features were used to characterize disease-metabolite associations. Finally, a random forest algorithm was employed to construct a model for identifying potential disease-metabolite associations., Results: The experimental results demonstrated that the proposed model achieved an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.968 in 5-fold cross-validations, while the Area Under the Precision-Recall Curve (AUPR) was 0.901, outperforming the vast majority of existing prediction methods. The case studies corroborated the majority of the novel associations identified by COM-RAN, thereby further demonstrating the reliability of the current method in predicting the potential relationship between metabolites and diseases., Conclusion: The COM-RAN model demonstrated promise in predicting associations between diseases and metabolites, suggesting that integrating knowledge graphs with machine learning methodologies can significantly improve the accuracy and reliability of predictions related to disease-associated metabolites., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

To address the incompleteness of knowledge graphs, multi-hop reasoning aims to find the unknown information from existing data and enhance the comprehensive understanding. The presence of reasoning paths endows multi-hop reasoning with interpretability and traceability. Existing reinforcement learning (RL)-based multi-hop reasoning methods primarily rely on the agent's blind trial-and-error approach in a large search space, which leads to inefficient training. In contrast, sequence-based multi-hop reasoning methods focus on learning the mapping from path to path to achieve better training efficiency, but they discard structured knowledge. The absence of structured knowledge directly hinders the ablity to capture and represent complex relations. To address the above issues, we propose a Dual View Graph Transformer Networks for Multi-hop Knowledge Graph Reasoning (DV4KGR), which enables the joint learning of structured and serialized views. The structured view contains a large amount of structured knowledge, which represents the relations among nodes from a global perspective. Meanwhile, the serialized view contains rich knowledge of reasoning semantics, aiding in training the mapping function from reasoning states to reasoning paths. We learn the representations of one-to-many relations in a supervised contrastive learning manner, which enhances the ability to represent complex relations. Additionally, we combine structured knowledge and rule induction for action smoothing, which effectively alleviates the overfitting problem associated with the end-to-end training mode. The experimental results on four benchmark datasets demonstrate that DV4KGR delivers better performance than the state-of-the-art baselines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.) more...

Implementing electronic health services with a patient-centric focus while adapting to the know-how of local contexts is a challenge. This paper addresses this challenge by establishing a template of modular requirements for designing a viable Electronic Health Record (EHR) system that enables transmission and sharing of patient data across primary, secondary, and specialized care, ensuring versatility in diverse healthcare environments and across varying socio-economic landscapes. The research is anchored in design science and employs an action research strategy, using northern Brazil as empirical case. The approach builds on generic requirements from standards established by the European Union, Fast Healthcare Interoperability Resources (FHIR), and the Swedish ePrescription journal system. These requirements are refined and adapted to the Brazilian context through a participatory method, considering development disparities across municipalities and aligning with national policy. A key feature is the integration of knowledge graphs, which, when combined with fieldwork iterations involving healthcare professionals and patient association representatives, facilitated the extraction of patient-centric requirements. Strategies from Brazilian healthcare policies targeting chronic kidney disease, selected as a significant challenge for specialized healthcare in emergent areas, were incorporated to generalize the design of EHR modules aimed at prevention and monitoring of population at risk. Results support that harmonization towards legacy system is strongly advised and discourage the introduction of systems designed from scratch., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval for the work reported on herein is not necessary according to the ethics regulations at Stockholm University. In particular, the work did not process special categories of personal data according to the EU Data Protection Regulation, i.e. personal data revealing racial or ethnic origin, political opinions, religious or philosophical beliefs or trade union membership and processing of genetic data, biometric data to uniquely identify a natural person, information about health or information about a natural person’s sex life or sexual orientation See https://medarbetare.su.se/forskning/etik-och-juridik/manniskor-och-personuppgifter/etikprovning-av-forskning-som-avser-manniskor for ethics regulations at Stockholm University . Informed consent was obtained from all participants involved in the study. Consent for publication: Not applicable, as this study does not include any identifiable human data or images. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).) more...

Advances in high-throughput genome sequencing have enabled large-scale genome sequencing in clinical practice and research studies. By analyzing genomic variants of humans, scientists can gain better understanding of the risk factors of complex diseases such as cancer and COVID-19. To model and analyze the rich genomic data, knowledge graphs (KGs) and graph machine learning (GML) can be regarded as enabling technologies. In this article, we present a scalable tool called VariantKG for analyzing genomic variants of humans modeled using KGs and GML. Specifically, we used publicly available genome sequencing data from patients with COVID-19. VariantKG extracts variant-level genetic information output by a variant calling pipeline, annotates the variant data with additional metadata, and converts the annotated variant information into a KG represented using the Resource Description Framework (RDF). The resulting KG is further enhanced with patient metadata and stored in a scalable graph database that enables efficient RDF indexing and query processing. VariantKG employs the Deep Graph Library (DGL) to perform GML tasks such as node classification. A user can extract a subset of the KG and perform inference tasks using DGL. The user can monitor the training and testing performance and hardware utilization. We tested VariantKG for KG construction by using 1,508 genome sequences, leading to 4 billion RDF statements. We evaluated GML tasks using VariantKG by selecting a subset of 500 sequences from the KG and performing node classification using well-known GML techniques such as GraphSAGE, Graph Convolutional Network (GCN) and Graph Transformer. VariantKG has intuitive user interfaces and features enabling a low barrier to entry for KG construction, model inference, and model interpretation on genomic variants of humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Prasanna, Kumar, Rao, Simoes and Rao.) more...

Background: Acute hepatic porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays of 15 years on average. The advent of electronic health records (EHR) data and machine learning (ML) may improve the timely recognition of rare diseases like AHP. However, prediction models can be difficult to train given the limited case numbers, unstructured EHR data, and selection biases intrinsic to healthcare delivery. We sought to train and characterize models for identifying patients with AHP., Methods: This diagnostic study used structured and notes-based EHR data from 2 centers at the University of California, UCSF (2012-2022) and UCLA (2019-2022). The data were split into 2 cohorts (referral and diagnosis) and used to develop models that predict (1) who will be referred for testing of acute porphyria, among those who presented with abdominal pain (a cardinal symptom of AHP), and (2) who will test positive, among those referred. The referral cohort consisted of 747 patients referred for testing and 99 849 contemporaneous patients who were not. The diagnosis cohort consisted of 72 confirmed AHP cases and 347 patients who tested negative. The case cohort was 81% female and 6-75 years old at the time of diagnosis. Candidate models used a range of architectures. Feature selection was semi-automated and incorporated publicly available data from knowledge graphs. Our primary outcome was the F-score on an outcome-stratified test set., Results: The best center-specific referral models achieved an F-score of 86%-91%. The best diagnosis model achieved an F-score of 92%. To further test our model, we contacted 372 current patients who lack an AHP diagnosis but were predicted by our models as potentially having it (≥10% probability of referral, ≥50% of testing positive). However, we were only able to recruit 10 of these patients for biochemical testing, all of whom were negative. Nonetheless, post hoc evaluations suggested that these models could identify 71% of cases earlier than their diagnosis date, saving 1.2 years., Conclusions: ML can reduce diagnostic delays in AHP and other rare diseases. Robust recruitment strategies and multicenter coordination will be needed to validate these models before they can be deployed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...

The remarkable success of Graph Neural Networks underscores their formidable capacity to assimilate multimodal inputs, markedly enhancing performance across a broad spectrum of domains. In the context of molecular modeling, considerable efforts have been made to enrich molecular representations by integrating data from diverse aspects. Nevertheless, current methodologies frequently compartmentalize geometric and semantic components, resulting in a fragmented approach that impairs the holistic integration of molecular attributes. This constrained scope limits the generalizability and efficacy of such models in downstream applications. A pivotal challenge lies in harmonizing heterogeneous data sources, particularly in addressing the inherent inconsistencies and sparsity within multimodal molecular datasets. To overcome these limitations, we present the Unified Knowledge-Guided Molecular Graph Encoder (UKGE), a groundbreaking framework that leverages heterogeneous graphs to unify the representation of diverse molecular modalities. Unlike prior methods, UKGE reconciles geometric and semantic features through the use of elemental knowledge graphs (KGs) and meta-path definitions by constructing Unified Molecular Graphs, enabling comprehensive and unified molecular representations. It employs an innovative Meta-Path Aware Message Passing mechanism within its molecular encoder, enhancing the integration of multimodal data. Additionally, a multi-task learning strategy balances data from different modalities, further enriching UKGE's capability to embed complex biological insights.Empirical evaluations highlight UKGE's excellence across tasks: DDI prediction achieves 96.91% ACC and 99.14% AUC in warm-start settings, with 83.15% ACC in cold-start scenarios. For CPI prediction, it reaches 0.644 CI on Davis and 0.659 on KIBA. In LBDD, it achieves 99.3% validity, 98.4% uniqueness, and 98.9% novelty, establishing UKGE as a state-of-the-art molecular modeling framework., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.) more...

Background: Rare diseases affect millions worldwide but sometimes face limited research focus individually due to low prevalence. Many rare diseases do not have specific International Classification of Diseases, Ninth Edition (ICD-9) and Tenth Edition (ICD-10), codes and therefore cannot be reliably extracted from granular fields like "Diagnosis" and "Problem List" entries, which complicates tasks that require identification of patients with these conditions, including clinical trial recruitment and research efforts. Recent advancements in large language models (LLMs) have shown promise in automating the extraction of medical information, offering the potential to improve medical research, diagnosis, and management. However, most LLMs lack professional medical knowledge, especially concerning specific rare diseases, and cannot effectively manage rare disease data in its various ontological forms, making it unsuitable for these tasks., Objective: Our aim is to create an end-to-end system called automated rare disease mining (AutoRD), which automates the extraction of rare disease-related information from medical text, focusing on entities and their relations to other medical concepts, such as signs and symptoms. AutoRD integrates up-to-date ontologies with other structured knowledge and demonstrates superior performance in rare disease extraction tasks. We conducted various experiments to evaluate AutoRD's performance, aiming to surpass common LLMs and traditional methods., Methods: AutoRD is a pipeline system that involves data preprocessing, entity extraction, relation extraction, entity calibration, and knowledge graph construction. We implemented this system using GPT-4 and medical knowledge graphs developed from the open-source Human Phenotype and Orphanet ontologies, using techniques such as chain-of-thought reasoning and prompt engineering. We quantitatively evaluated our system's performance in entity extraction, relation extraction, and knowledge graph construction. The experiment used the well-curated dataset RareDis2023, which contains medical literature focused on rare disease entities and their relations, making it an ideal dataset for training and testing our methodology., Results: On the RareDis2023 dataset, AutoRD achieved an overall entity extraction F1-score of 56.1% and a relation extraction F1-score of 38.6%, marking a 14.4% improvement over the baseline LLM. Notably, the F1-score for rare disease entity extraction reached 83.5%, indicating high precision and recall in identifying rare disease mentions. These results demonstrate the effectiveness of integrating LLMs with medical ontologies in extracting complex rare disease information., Conclusions: AutoRD is an automated end-to-end system for extracting rare disease information from text to build knowledge graphs, addressing critical limitations of existing LLMs by improving identification of these diseases and connecting them to related clinical features. This work underscores the significant potential of LLMs in transforming health care, particularly in the rare disease domain. By leveraging ontology-enhanced LLMs, AutoRD constructs a robust medical knowledge base that incorporates up-to-date rare disease information, facilitating improved identification of patients and resulting in more inclusive research and trial candidacy efforts., (© Lang Cao, Jimeng Sun, Adam Cross. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).) more...

This study explores the possibility of integrating and retrieving heterogenous data across platforms by using ontology graph databases to enhance educational insights and enabling advanced data-driven decision-making. Motivated by some of the well-known universities and other Higher Education Institutions ontology, this study improvises the existing entities and introduces new entities in order to tackle a new topic identified from the preliminary interview conducted in the study to cover the study objective. The paper also proposes an innovative ontology, referred to as Student Performance and Course, to enhance resource management and evaluation mechanisms on course, students, and MOOC performance by the faculty. The model solves the issues of data accumulation and their heterogeneity, including the problem of having data in different formats and various semantic similarities, and is suitable for processing large amounts of data in terms of scalability. Thus, it also offers a way to confirm the process of data retrieval that is based on performance assessment with the help of an evaluation matrix., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.) more...

Computational representations of knowledge graphs are critical for several tasks in bioinformatics, including large-scale graph analysis and gene function characterization. In this study, we introduce gGN, an unsupervised neural network for learning node representations as Gaussian distributions. Unlike prior efforts, where the covariance matrices of these distributions are simplified to diagonal, we propose representing them with a low-rank approximation. This representation not only maintains manageable learning complexity, allowing for scaling to large graphs, but is also more effective for modeling the structural features of knowledge graphs, such as their hierarchical and directional relationships between nodes. To learn the low-rank Gaussian distributions, we introduce a semantic-based loss function that effectively preserves these structural features. Systematic experiments reveal that gGN preserves structural features more effectively than existing approaches and scales efficiently on large knowledge graphs. Furthermore, applying gGN to represent the Gene Ontology, a widely used knowledge graph in bioinformatics, outperformed multiple baseline methods in ubiquitous gene characterization tasks. Altogether, the proposed low-rank Gaussian distributions not only effectively represent knowledge graphs but also open new avenues for enhancing bioinformatics tasks. gGN is publicly available as an easily installable package at https://github.com/aedera/ggn., Competing Interests: Declaration of competing interest None Declared, (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...

Brand advocates, characterized by their enthusiasm for promoting a brand without incentives, play a crucial role in driving positive word-of-mouth (WOM) and influencing potential customers. However, there is a notable lack of intelligent systems capable of accurately identifying online advocates based on their social interactions with brands. Knowledge Graphs (KGs) offer structured and factual representations of human knowledge, providing a potential solution to gain holistic insights into customer preferences and interactions with a brand. This study presents a novel framework that leverages KG construction and embedding techniques to identify brand advocates accurately. By harnessing the power of KGs, our framework enhances the accuracy and efficiency of identifying and understanding brand advocates, providing valuable insights into customer advocacy dynamics in the online realm. Moreover, we address the critical aspect of social credibility, which significantly influences the impact of advocacy efforts. Incorporating social credibility analysis into our framework allows businesses to identify and mitigate spammers, preserving authenticity and customer trust. To achieve this, we incorporate and extend DSpamOnto, a specialized ontology designed to identify social spam, with a focus on the social commerce domain. Additionally, we employ cutting-edge embedding techniques to map the KG into a low-dimensional vector space, enabling effective link prediction, clustering, and visualization. Through a rigorous evaluation process, we demonstrate the effectiveness and performance of our proposed framework, highlighting its potential to empower businesses in cultivating brand advocates and driving meaningful customer engagement strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abu-Salih, Alotaibi, Al-Okaily, Aljaafari and Almiani.) more...

Entity alignment is a crucial task in knowledge graphs, aiming to match corresponding entities from different knowledge graphs. Due to the scarcity of pre-aligned entities in real-world scenarios, research focused on unsupervised entity alignment has become more popular. However, current unsupervised entity alignment methods suffer from a lack of informative entity guidance, hindering their ability to accurately predict challenging entities with similar names and structures. To solve these problems, we present an unsupervised multi-view contrastive learning framework with an attention-based reranking strategy for entity alignment, named AR-Align. In AR-Align, two kinds of data augmentation methods are employed to provide a complementary view for neighborhood and attribute, respectively. Next, a multi-view contrastive learning method is introduced to reduce the semantic gap between different views of the augmented entities. Moreover, an attention-based reranking strategy is proposed to rerank the hard entities through calculating their weighted sum of embedding similarities on different structures. Experimental results indicate that AR-Align outperforms most both supervised and unsupervised state-of-the-art methods on three benchmark datasets., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...

Background: Accurate prediction of compound-protein interaction (CPI) plays a crucial role in drug discovery. Existing data-driven methods aim to learn from the chemical structures of compounds and proteins yet ignore the conceptual knowledge that is the interrelationships among the fundamental elements in the biomedical knowledge graph (KG). Knowledge graphs provide a comprehensive view of entities and relationships beyond individual compounds and proteins. They encompass a wealth of information like pathways, diseases, and biological processes, offering a richer context for CPI prediction. This contextual information can be used to identify indirect interactions, infer potential relationships, and improve prediction accuracy. In real-world applications, the prevalence of knowledge-missing compounds and proteins is a critical barrier for injecting knowledge into data-driven models., Results: Here, we propose BEACON, a data and knowledge dual-driven framework that bridges chemical structure and conceptual knowledge for CPI prediction. The proposed BEACON learns the consistent representations by maximizing the mutual information between chemical structure and conceptual knowledge and predicts the missing representations by minimizing their conditional entropy. BEACON achieves state-of-the-art performance on multiple datasets compared to competing methods, notably with 5.1% and 6.6% performance gain on the BIOSNAP and DrugBank datasets, respectively. Moreover, BEACON is the only approach capable of effectively predicting knowledge representations for knowledge-lacking compounds and proteins., Conclusions: Overall, our work provides a general approach for directly injecting conceptual knowledge to enhance the performance of CPI prediction., (© 2024. The Author(s).) more...

Medicine recommendation systems are designed to aid healthcare professionals by analysing a patient's admission data to recommend safe and effective medications. These systems are categorised into two types: instance-based and longitudinal-based. Instance-based models only consider the current admission, while longitudinal models consider the patient's medical history. Electronic Health Records are used to incorporate medical history into longitudinal models. This project proposes a novel Knowledge Graph-Driven Medicine Recommendation System using Graph Neural Networks, KGDNet, that utilises longitudinal EHR data along with ontologies and Drug-Drug Interaction knowledge to construct admission-wise clinical and medicine Knowledge Graphs for every patient. Recurrent Neural Networks are employed to model a patient's historical data, and Graph Neural Networks are used to learn embeddings from the Knowledge Graphs. A Transformer-based Attention mechanism is then used to generate medication recommendations for the patient, considering their current clinical state, medication history, and joint medical records. The model is evaluated on the MIMIC-IV EHR data and outperforms existing methods in terms of precision, recall, F1 score, Jaccard score, and Drug-Drug Interaction control. An ablation study on our models various inputs and components to provide evidence for the importance of each component in providing the best performance. Case study is also performed to demonstrate the real-world effectiveness of KGDNet., (© 2024. The Author(s).) more...

Background: Ontologies are fundamental components of informatics infrastructure in domains such as biomedical, environmental, and food sciences, representing consensus knowledge in an accurate and computable form. However, their construction and maintenance demand substantial resources and necessitate substantial collaboration between domain experts, curators, and ontology experts. We present Dynamic Retrieval Augmented Generation of Ontologies using AI (DRAGON-AI), an ontology generation method employing Large Language Models (LLMs) and Retrieval Augmented Generation (RAG). DRAGON-AI can generate textual and logical ontology components, drawing from existing knowledge in multiple ontologies and unstructured text sources., Results: We assessed performance of DRAGON-AI on de novo term construction across ten diverse ontologies, making use of extensive manual evaluation of results. Our method has high precision for relationship generation, but has slightly lower precision than from logic-based reasoning. Our method is also able to generate definitions deemed acceptable by expert evaluators, but these scored worse than human-authored definitions. Notably, evaluators with the highest level of confidence in a domain were better able to discern flaws in AI-generated definitions. We also demonstrated the ability of DRAGON-AI to incorporate natural language instructions in the form of GitHub issues., Conclusions: These findings suggest DRAGON-AI's potential to substantially aid the manual ontology construction process. However, our results also underscore the importance of having expert curators and ontology editors drive the ontology generation process., (© 2024. The Author(s).) more...

Given the widespread presence of micropollutants in urban water systems, it is imperative to gain a comprehensive understanding of their degradation pathways. This paper focuses on sulfamethoxazole (SMX) as a model molecule due to its extensive study, aiming to elucidate its degradation pathways in biological (BIO) and oxidative (AOP) processes. Numerous reaction pathways are outlined in scientific papers. However, a significant deficiency in current methodologies has led to the development of a novel meta-analytical approach, seeking consensus among researchers by synthesizing data from studies characterized by their heterogeneity and contradictions. As an innovative alternative, probabilistic graphical models such as Bayesian networks (BNs) could illuminate the relationships and dependencies between various transformation products, providing a holistic view of the degradation process. Based on the analysis of an extensive bibliography gathering more than 45 articles for more than 140 molecules and 177 reaction pathways, this study proposes a meta-analysis methodology based on Bayesian networks., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Inductive link prediction (ILP) in knowledge graphs (KGs) aims to predict missing links between entities that were not seen during the training phase. Recent some subgraph-based methods have shown some advancements, but they all overlook the relational semantics between entities during subgraph extraction. To overcome this limitation, we introduce a novel inductive link prediction model named SASILP (Structure and Semantic Inductive Link Prediction), which comprehensively incorporates relational semantics in both subgraph extraction and node initialization processes. The model employs a random walk strategy to calculate the structural scores of neighboring nodes and utilizes an enhanced graph attention network to determine their semantic scores. By integrating both structural and semantic scores, SASILP strategically selects key nodes to form a subgraph. Furthermore, the subgraph is initialized with a node initialization technique that integrates information about neighboring relations. The experiments conducted on benchmark datasets demonstrate that SASILP outperforms state-of-the-art methods on inductive link prediction tasks, and verify the effectiveness of our approach., Competing Interests: The authors declare there are no competing interests., (©2024 Liu et al.) more...

Knowledge graph reasoning, vital for addressing incompleteness and supporting applications, faces challenges with the continuous growth of graphs. To address this challenge, several inductive reasoning models for encoding emerging entities have been proposed. However, they do not consider the multi-batch emergence scenario, where new entities and new facts are usually added to knowledge graphs (KGs) in multiple batches in the order of their emergence. To simulate the continuous growth of knowledge graphs, a novel multi-batch emergence (MBE) scenario has recently been proposed. We propose a path-based inductive model to handle multi-batch entity growth, enhancing entity encoding with type information. Specifically, we observe a noteworthy pattern in which entity types at the head and tail of the same relation exhibit relative regularity. To utilize this regularity, we introduce a pair of learnable parameters for each relation, representing entity type features linked to the relation. The type features are dedicated to encoding and updating the features of entities. Meanwhile, our model incorporates a novel attention mechanism, combining statistical co-occurrence and semantic similarity of relations effectively for contextual information capture. After generating embeddings, we employ reinforcement learning for path reasoning. To reduce sparsity and expand the action space, our model generates soft candidate facts by grounding a set of soft path rules. Meanwhile, we incorporate the confidence scores of these facts in the action space to facilitate the agent to better distinguish between original facts and rule-generated soft facts. Performances on three multi-batch entity growth datasets demonstrate robust performance, consistently outperforming state-of-the-art models., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...

Feature selection in Knowledge Graphs (KGs) is increasingly utilized in diverse domains, including biomedical research, Natural Language Processing (NLP), and personalized recommendation systems. This paper delves into the methodologies for feature selection (FS) within KGs, emphasizing their roles in enhancing machine learning (ML) model efficacy, hypothesis generation, and interpretability. Through this comprehensive review, we aim to catalyze further innovation in FS for KGs, paving the way for more insightful, efficient, and interpretable analytical models across various domains. Our exploration reveals the critical importance of scalability, accuracy, and interpretability in FS techniques, advocating for the integration of domain knowledge to refine the selection process. We highlight the burgeoning potential of multi-objective optimization and interdisciplinary collaboration in advancing KG FS, underscoring the transformative impact of such methodologies on precision medicine, among other fields. The paper concludes by charting future directions, including the development of scalable, dynamic FS algorithms and the integration of explainable AI principles to foster transparency and trust in KG-driven models., (© The Author(s) 2024. Published by Oxford University Press.) more...

Drug repurposing has emerged as a effective and efficient strategy to identify new treatments for a variety of diseases. One of the most effective approaches for discovering potential new drug candidates involves the utilization of Knowledge Graphs (KGs). This review comprehensively explores some of the most prominent KGs, detailing their structure, data sources, and how they facilitate the repurposing of drugs. In addition to KGs, this paper delves into various artificial intelligence techniques that enhance the process of drug repurposing. These methods not only accelerate the identification of viable drug candidates but also improve the precision of predictions by leveraging complex datasets and advanced algorithms. Furthermore, the importance of explainability in drug repurposing is emphasized. Explainability methods are crucial as they provide insights into the reasoning behind AI-generated predictions, thereby increasing the trustworthiness and transparency of the repurposing process. We will discuss several techniques that can be employed to validate these predictions, ensuring that they are both reliable and understandable., (© The Author(s) 2024. Published by Oxford University Press.) more...

Artificial Intelligence (AI), particularly Machine Learning (ML), has gained attention for its potential in various domains. However, approaches integrating symbolic AI with ML on Knowledge Graphs have not gained significant focus yet. We argue that exploiting RDF/OWL semantics while conducting ML could provide useful insights. We present a use case using signaling pathways from the Reactome database to explore drug safety. Promising outcomes suggest the need for further investigation and collaboration with domain experts. more...

Biomedical data analysis and visualization often demand data experts for each unique health event. There is a clear lack of automatic tools for semantic visualization of the spread of health risks through biomedical data. Illnesses such as coronavirus disease (COVID-19) and Monkeypox spread rampantly around the world before governments could make decisions based on the analysis of such data. We propose the design of a knowledge graph (KG) for spatio-temporal tracking of public health event propagation. To achieve this, we propose the specialization of the Core Propagation Phenomenon Ontology (PropaPhen) into a health-related propagation phenomenon domain ontology. Data from the UMLS and OpenStreetMaps are suggested for instantiating the proposed knowledge graph. Finally, the results of a use case on COVID-19 data from the World Health Organization are analyzed to evaluate the possibilities of our approach. more...

Health literacy empowers people to access, understand and apply health information to effectively manage their own health and to be an active participant in healthcare decisions. In this paper we propose a conceptual model for cognitive factors affecting health literacy and related socioeconomic aspects. Then we develop the HEALIE Knowledge Graph to represent the model, drawing from various medical ontologies, resources, and insights from domain experts. Finally, we combine the Knowledge Graph with a Large Language Model to generate personalised medical content and showcase the results through an example. more...

Real-world data (RWD) (i.e., data from Electronic Healthcare Records - EHRs, ePrescription systems, patient registries, etc.) gain increasing attention as they could support observational studies on a large scale. OHDSI is one of the most prominent initiatives regarding the harmonization of RWD and the development of relevant tools via the use of a common data model, OMOP-CDM. OMOP-CDM is a crucial step towards syntactic and semantic data interoperability. Still, OMOP-CDM is based on a typical relational database format, and thus, the vision of a fully connected semantically enriched model is not fully realized. This work presents an open-source effort to map the OMOP-CDM model and the data it hosts, to an ontological model using RDF to support the FAIRness of RWD and their interlinking with Linked Open Data (LOD) towards the vision of the Semantic Web. more...

The rapid expansion of multi-omics data has transformed biological research, offering unprecedented opportunities to explore complex genomic relationships across diverse organisms. However, the vast volume and heterogeneity of these datasets presents significant challenges for analyses. Here we introduce SocialGene, a comprehensive software suite designed to collect, analyze, and organize multi-omics data into structured knowledge graphs, with the ability to handle small projects to repository-scale analyses. Originally developed to enhance genome mining for natural product drug discovery, SocialGene has been effective across various applications, including functional genomics, evolutionary studies, and systems biology. SocialGene's concerted Python and Nextflow libraries streamline data ingestion, manipulation, aggregation, and analysis, culminating in a custom Neo4j database. The software not only facilitates the exploration of genomic synteny but also provides a foundational knowledge graph supporting the integration of additional diverse datasets and the development of advanced search engines and analyses. This manuscript introduces some of SocialGene's capabilities through brief case studies including targeted genome mining for drug discovery, accelerated searches for similar and distantly related biosynthetic gene clusters in biobank-available organisms, integration of chemical and analytical data, and more. SocialGene is free, open-source, MIT-licensed, designed for adaptability and extension, and available from github.com/socialgene. more...

In clinical artificial intelligence (AI), graph representation learning, mainly through graph neural networks and graph transformer architectures, stands out for its capability to capture intricate relationships and structures within clinical datasets. With diverse data-from patient records to imaging-graph AI models process data holistically by viewing modalities and entities within them as nodes interconnected by their relationships. Graph AI facilitates model transfer across clinical tasks, enabling models to generalize across patient populations without additional parameters and with minimal to no retraining. However, the importance of human-centered design and model interpretability in clinical decision-making cannot be overstated. Since graph AI models capture information through localized neural transformations defined on relational datasets, they offer both an opportunity and a challenge in elucidating model rationale. Knowledge graphs can enhance interpretability by aligning model-driven insights with medical knowledge. Emerging graph AI models integrate diverse data modalities through pretraining, facilitate interactive feedback loops, and foster human-AI collaboration, paving the way toward clinically meaningful predictions. more...

Drug repurposing refers to the inference of therapeutic relationships between a clinical indication and existing compounds. As an emerging paradigm in drug development, drug repurposing enables more efficient treatment of rare diseases, stratified patient populations, and urgent threats to public health. However, prioritizing well-suited drug candidates from among a nearly infinite number of repurposing options continues to represent a significant challenge in drug development. Over the past decade, advances in genomic profiling, database curation, and machine learning techniques have enabled more accurate identification of drug repurposing candidates for subsequent clinical evaluation. This review outlines the major methodologic classes that these approaches comprise, which rely on ( a ) protein structure, ( b ) genomic signatures, ( c ) biological networks, and ( d ) real-world clinical data. We propose that realizing the full impact of drug repurposing methodologies requires a multidisciplinary understanding of each method's advantages and limitations with respect to clinical practice. more...

Personalized learning resource recommendations may help resolve the difficulties of online education that include learning mazes and information overload. However, existing personalized learning resource recommendation algorithms have shortcomings such as low accuracy and low efficiency. This study proposes a deep recommendation system algorithm based on a knowledge graph (D-KGR) that includes four data processing units. These units are the recommendation unit (RS unit), the knowledge graph feature representation unit (KGE unit), the cross compression unit (CC unit), and the feature extraction unit (FE unit). This model integrates technologies including the knowledge graph, deep learning, neural network, and data mining. It introduces cross compression in the feature learning process of the knowledge graph and predicts user attributes. Multimodal technology is used to optimize the process of project attribute processing; text type attributes, multivalued type attributes, and other type attributes are processed separately to reconstruct the knowledge graph. A convolutional neural network algorithm is introduced in the reconstruction process to optimize the data feature qualities. Experimental analysis was conducted from two aspects of algorithm efficiency and accuracy, and the particle swarm optimization, neural network, and knowledge graph algorithms were compared. Several tests showed that the deep recommendation system algorithm had obvious advantages when the number of learning resources and users exceeded 1,000. It has the ability to integrate systems such as the particle swarm optimization iterative classification, neural network intelligent simulation, and low resource consumption. It can quickly process massive amounts of information data, reduce algorithm complexity and requires less time and had lower costs. Our algorithm also has better efficiency and accuracy., Competing Interests: Xiao Feng Ma is an employee of Chengfang Technology Co., Ltd., (© 2024 Wang et al.) more...

Background: The medical knowledge graph provides explainable decision support, helping clinicians with prompt diagnosis and treatment suggestions. However, in real-world clinical practice, patients visit different hospitals seeking various medical services, resulting in fragmented patient data across hospitals. With data security issues, data fragmentation limits the application of knowledge graphs because single-hospital data cannot provide complete evidence for generating precise decision support and comprehensive explanations. It is important to study new methods for knowledge graph systems to integrate into multicenter, information-sensitive medical environments, using fragmented patient records for decision support while maintaining data privacy and security., Objective: This study aims to propose an electronic health record (EHR)-oriented knowledge graph system for collaborative reasoning with multicenter fragmented patient medical data, all the while preserving data privacy., Methods: The study introduced an EHR knowledge graph framework and a novel collaborative reasoning process for utilizing multicenter fragmented information. The system was deployed in each hospital and used a unified semantic structure and Observational Medical Outcomes Partnership (OMOP) vocabulary to standardize the local EHR data set. The system transforms local EHR data into semantic formats and performs semantic reasoning to generate intermediate reasoning findings. The generated intermediate findings used hypernym concepts to isolate original medical data. The intermediate findings and hash-encrypted patient identities were synchronized through a blockchain network. The multicenter intermediate findings were collaborated for final reasoning and clinical decision support without gathering original EHR data., Results: The system underwent evaluation through an application study involving the utilization of multicenter fragmented EHR data to alert non-nephrology clinicians about overlooked patients with chronic kidney disease (CKD). The study covered 1185 patients in nonnephrology departments from 3 hospitals. The patients visited at least two of the hospitals. Of these, 124 patients were identified as meeting CKD diagnosis criteria through collaborative reasoning using multicenter EHR data, whereas the data from individual hospitals alone could not facilitate the identification of CKD in these patients. The assessment by clinicians indicated that 78/91 (86%) patients were CKD positive., Conclusions: The proposed system was able to effectively utilize multicenter fragmented EHR data for clinical application. The application study showed the clinical benefits of the system with prompt and comprehensive decision support., (©Yong Shang, Yu Tian, Kewei Lyu, Tianshu Zhou, Ping Zhang, Jianghua Chen, Jingsong Li. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 05.07.2024.) more...

Purpose: This work aims to demystify Knowledge Graphs (KGs) in pharmacovigilance (PV). It complements the scoping review within this issue. By bridging knowledge gaps and stimulating interest, further engagement with this topic by pharmacovigilance professionals will be facilitated., Methods: We elucidate fundamental KGs concepts and terminology, followed by delineating a sequence of implementation steps: use case definition, data type selection, data sourcing, KG construction, KG embedding, and deriving actionable insights. Information technology options and limitations are also explored., Findings: KGs in pharmacovigilance is a multi-disciplinary field involving information technology, machine learning, biology, and PV. We were able to synthesize the relevant core concepts to create an intuitive exposition of KGs in PV., Implications: This work demystifies KGs with a pharmacovigilance focus, preparing readers for the accompanying in-depth scoping review. that follows. It lays the groundwork for advancing PV research and practice by emphasizing the importance of engaging with vigilance experts. This approach enhances knowledge sharing and collaboration, contributing to more effective and informed pharmacovigilance efforts and optimal assessment and deployment of KGs in PV., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Manfred Hauben is a former employee of Pfizer Inc. and owns Pfizer stocks and stock options as well as stocks in other pharmaceutical companies that manufacture or market drugs mentioned in this article. Manfred Hauben has no other conflicts of interest that are relevant to the content of this manuscript. Mazin Rafi is a former Summer Associate of Pfizer Incorporate, and is currently pursuing an MSc in Data Science through Rutgers University. Mazin Rafi has no other conflicts of interest that are relevant to the content of this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) more...

Purpose: To critically assess the role and added value of knowledge graphs in pharmacovigilance, focusing on their ability to predict adverse drug reactions., Methods: A systematic scoping review was conducted in which detailed information, including objectives, technology, data sources, methodology, and performance metrics, were extracted from a set of peer-reviewed publications reporting the use of knowledge graphs to support pharmacovigilance signal detection., Findings: The review, which included 47 peer-reviewed articles, found knowledge graphs were utilized for detecting/predicting single-drug adverse reactions and drug-drug interactions, with variable reported performance and sparse comparisons to legacy methods., Implications: Research to date suggests that knowledge graphs have the potential to augment predictive signal detection in pharmacovigilance, but further research using more reliable reference sets of adverse drug reactions and comparison with legacy pharmacovigilance methods are needed to more clearly define best practices and to establish their place in holistic pharmacovigilance systems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: At the time of manuscript submission Manfred Hauben was a full time employee of Pfizer Inc., New York, New York, USA; he has also won stocks in pharmaceutical companies that may manufacture or market drugs mentioned in the article. However, he reports no other conflicts of interest that are directly relevant to the content of this manuscript. Mazin Rafi, a former Summer Associate of Pfizer Incorporated, is currently pursuing an MSc in Data Science through Rutgers University, New Brunswick, USA. He has no other conflicts of interest that are relevant to the content of this manuscript. Ibrahim Abdelaziz is affiliated with IBM Research - Yorktown Heights, Yorktown Heights, NY, USA. He reports no conflicts of interest that are relevant to the content of this manuscript. Oktie Hassanzadeh is also affiliated with IBM Research - Yorktown Heights, Yorktown Heights, NY, USA. He reports no conflicts of interest that are relevant to the content of this manuscript., (Published by Elsevier Inc.) more...

Major depressive disorder (MDD) is a debilitating mental health condition that poses significant risks and burdens. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a promising tool in investigating the neural mechanisms underlying MDD. However, a comprehensive bibliometric analysis of resting-state fMRI in MDD is currently lacking. Here, we aimed to thoroughly explore the trends and frontiers of resting-state fMRI in MDD research. The relevant publications were retrieved from the Web of Science database for the period between 1998 and 2022, and the CiteSpace software was employed to identify the influence of authors, institutions, countries/regions, and the latest research trends. A total of 1501 publications met the search criteria, revealing a gradual increase in the number of annual publications over the years. China contributed the largest publication output, accounting for the highest percentage among all countries. Particularly, the University of Electronic Science and Technology of China, Capital Medical University, and Harvard Medical School were identified as key institutions that have made substantial contributions to this growth. Neuroimage, Biological Psychiatry, Journal of Affective Disorders, and Proceedings of the National Academy of Sciences of the United States of America are among the influential journals in the field of resting-state fMRI research in MDD. Burst keywords analysis suggest the emerging research frontiers in this field are characterized by prominent keywords such as dynamic functional connectivity, cognitive control network, transcranial brain stimulation, and childhood trauma. Overall, our study provides a systematic overview into the historical development, current status, and future trends of resting-state fMRI in MDD, thus offering a useful guide for researchers to plan their future research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.) more...

Purpose: Granulomatous mastitis (GLM) is a rare and complex chronic inflammatory disease of the breast with an unknown cause and a tendency to recur. As medical science advances, the cause, treatment strategies, and comprehensive management of GLM have increasingly attracted widespread attention. The aim of this study is to assess the development trends and research focal points in the GLM field over the past 24 years using bibliometric analysis., Methods: Using GLM, Granulomatous mastitis (GM), Idiopathic granulomatous lobular mastitis (IGLM), and Idiopathic granulomatous mastitis (IGM) as keywords, we retrieved publications related to GLM from 2000 to 2023 from the Web of Science, excluding articles irrelevant to this study. Citespace and VOSviewer were employed for data analysis and visualization., Results: A total of 347 publications were included in this analysis. Over the past 24 years, the number of publications has steadily increased, with Turkey being the leading contributor in terms of publications and citations. The University of Health Sciences, Istanbul University, and Istanbul University Cerrahpasa were the most influential institutions. The Breast Journal, Breast Care, and Journal of Investigative Surgery were the journals that published the most on this topic. The research primarily focused on the cause, differential diagnosis, treatment, and comprehensive management of GLM. Issues related to recurrence, hyperprolactinemia, and Corynebacterium emerged as current research hotspots., Conclusion: Our bibliometric study outlines the historical development of the GLM field and identifies recent research focuses and trends, which may aid researchers in identifying research hotspots and directions, thereby advancing the study of GLM., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhang et al.) more...

Numerous methods and pipelines have recently emerged for the automatic extraction of knowledge graphs from documents such as scientific publications and patents. However, adapting these methods to incorporate alternative text sources like micro-blogging posts and news has proven challenging as they struggle to model open-domain entities and relations, typically found in these sources. In this paper, we propose an enhanced information extraction pipeline tailored to the extraction of a knowledge graph comprising open-domain entities from micro-blogging posts on social media platforms. Our pipeline leverages dependency parsing and classifies entity relations in an unsupervised manner through hierarchical clustering over word embeddings. We provide a use case on extracting semantic triples from a corpus of 100 thousand tweets about digital transformation and publicly release the generated knowledge graph. On the same dataset, we conduct two experimental evaluations, showing that the system produces triples with precision over 95% and outperforms similar pipelines of around 5% in terms of precision, while generating a comparatively higher number of triples., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Diego Reforgiato Recupero is an associate Editor of the Information Science section at the Heliyon journal., (© 2024 The Author(s).) more...

Objective: Designing a new clinical trial entails many decisions, such as defining a cohort and setting the study objectives to name a few, and therefore can benefit from recommendations based on exhaustive mining of past clinical trial records. This study proposes an approach based on knowledge graph embeddings and semantics-driven inductive inference for generating such recommendations., Method: The proposed recommendation methodology is based on neural embeddings trained on first-of-its-kind knowledge graph constructed from clinical trials data. The methodology includes design of a knowledge graph for clinical trial data, evaluation of various knowledge graph embedding techniques for it, application of a novel inductive inference method using these embeddings, and generation of recommendations for clinical trial design. The study uses freely available data from clinicaltrials.gov and related sources., Results: The proposed approach for recommendations obtained relevance scores ranging from 70% to 83%. These scores were determined by evaluating the text similarity of recommended elements to actual elements used in clinical trials that are in progress. Furthermore, the most pertinent recommendations were consistently located towards the top of the list, indicating the effectiveness of our method., Conclusion: Our study suggests that inductive inference using node semantics is a viable approach for generating recommendations using graphs neural embeddings, and that there is a potential for improvement in training graph embeddings using node semantics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.) more...

Recent years have witnessed increasing interest in the few-shot knowledge graph completion due to its potential to augment the coverage of few-shot relations in knowledge graphs. Existing methods often use the one-hop neighbors of the entity to enhance its embedding and match the query instance and support set at the instance level. However, such methods cannot handle inter-neighbor interaction, local entity matching and the varying significance of feature dimensions. To bridge this gap, we propose the Multi-Level Attention-enhanced matching Network (MuLAN) for few-shot knowledge graph completion. In MuLAN, a multi-head self-attention neighbor encoder is designed to capture the inter-neighbor interaction and learn the entity embeddings. Then, entity-level attention and instance-level attention are responsible for matching the query instance and support set from the local and global perspectives, respectively, while feature-level attention is utilized to calculate the weights of the feature dimensions. Furthermore, we design a consistency constraint to ensure the support instance embeddings are close to each other. Extensive experiments based on two well-known datasets (i.e., NELL-One and Wiki-One) demonstrate significant advantages of MuLAN over 11 state-of-the-art competitors. Compared to the best-performing baseline, MuLAN achieves 14.5% higher MRR and 13.3% higher Hits@K on average., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...

Objectives: This study focuses on refining temporal relation extraction within medical documents by introducing an innovative bimodal architecture. The overarching goal is to enhance our understanding of narrative processes in the medical domain, particularly through the analysis of extensive reports and notes concerning patient experiences., Materials and Methods: Our approach involves the development of a bimodal architecture that seamlessly integrates information from both text documents and knowledge graphs. This integration serves to infuse common knowledge about events into the temporal relation extraction process. Rigorous testing was conducted on diverse clinical datasets, emulating real-world scenarios where the extraction of temporal relationships is paramount., Results: The performance of our proposed bimodal architecture was thoroughly evaluated across multiple clinical datasets. Comparative analyses demonstrated its superiority over existing methods reliant solely on textual information for temporal relation extraction. Notably, the model showcased its effectiveness even in scenarios where not provided with additional information., Discussion: The amalgamation of textual data and knowledge graph information in our bimodal architecture signifies a notable advancement in the field of temporal relation extraction. This approach addresses the critical need for a more profound understanding of narrative processes in medical contexts., Conclusion: In conclusion, our study introduces a pioneering bimodal architecture that harnesses the synergy of text and knowledge graph data, exhibiting superior performance in temporal relation extraction from medical documents. This advancement holds significant promise for improving the comprehension of patients' healthcare journeys and enhancing the overall effectiveness of extracting temporal relationships in complex medical narratives., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.) more...

The Canadian Census of Population is a survey that collects statistical information on the Canadian population. These censuses contain valuable socioeconomic data that is often used by both the public and private sectors for project planning and decision-making. However, there are a few issues that may arise when using census data. Firstly, data wrangling, which is often a time-consuming process, needs to be conducted in order to clean and prepare the data for integration and use. Secondly, different datasets across different census years may be using different terms to describe the same concept/entity, hence creating a problem of referential equivalence (i.e., how do we know whether two different datasets are referring to the same concepts/entities?). Lastly, the data found in a census is often described using natural language that isn't easily interpreted by machines and can be difficult to break down or deconstruct. In this paper, we develop and propose the use of an ontology for representing the data from the Canadian Census of Population as linked data in order to address the aforementioned issues, evaluate the ontology using competency questions based on real world use cases, and discuss the advantages of census linked data for integration and visualisation uses., Competing Interests: Statement on conflicts of interest: The authors declare that there are no known conflicts of interest. more...

Leveraging AI for synthesizing the deluge of biomedical knowledge has great potential for pharmacological discovery with applications including developing new therapeutics for untreated diseases and repurposing drugs as emergent pandemic treatments. Creating knowledge graph representations of interacting drugs, diseases, genes, and proteins enables discovery via embedding-based ML approaches and link prediction. Previously, it has been shown that these predictive methods are susceptible to biases from network structure, namely that they are driven not by discovering nuanced biological understanding of mechanisms, but based on high-degree hub nodes. In this work, we study the confounding effect of network topology on biological relation semantics by creating an experimental pipeline of knowledge graph semantic and topological perturbations. We show that the drop in drug repurposing performance from ablating meaningful semantics increases by 21% and 38% when mitigating topological bias in two networks. We demonstrate that new methods for representing knowledge and inferring new knowledge must be developed for making use of biomedical semantics for pharmacological innovation, and we suggest fruitful avenues for their development., (© 2024. The Author(s).) more...

In the highly competitive field of material manufacturing, stakeholders strive for the increased quality of the end products, reduced cost of operation, and the timely completion of their business processes. Digital twin (DT) technologies are considered major enablers that can be deployed to assist the development and effective provision of manufacturing processes. Additionally, knowledge graphs (KG) have emerged as efficient tools in the industrial domain and are able to efficiently represent data from various disciplines in a structured manner while also supporting advanced analytics. This paper proposes a solution that integrates a KG and DTs. Through this synergy, we aimed to develop highly autonomous and flexible DTs that utilize the semantic knowledge stored in the KG to better support advanced functionalities. The developed KG stores information about materials and their properties and details about the processes in which they are involved, following a flexible schema that is not domain specific. The DT comprises smaller Virtual Objects (VOs), each one acting as an abstraction of a single step of the Industrial Business Process (IBP), providing the necessary functionalities that simulate the corresponding real-world process. By executing appropriate queries to the KG, the DT can orchestrate the operation of the VOs and their physical counterparts and configure their parameters accordingly, in this way increasing its self-awareness. In this article, the architecture of such a solution is presented and its application in a real laser glass bending process is showcased. more...

In the dynamic landscape of modern education, the search for improved pedagogical methods, enriched learning experiences, and empowered educators remains a perpetual pursuit. In recent years, a remarkable technological innovation has asserted its dominance in education: Knowledge Graphs (KGs). These structured representations of knowledge are increasingly proving to be indispensable tools, fostering advancements driven by the growing recognition of their essential role in enriching personalised learning, curriculum design, concept mapping, and educational content recommendation systems. In this paper, a systematic literature review (SLR) has been conducted to comprehensively examine KG construction methodologies and their applications across five key domains in education. In each examined study, we highlight the specific KG functionalities, knowledge extraction techniques, knowledge base characteristics, resource requirements, evaluation criteria, and limitations. This paper distinguishes itself by offering a broad overview of KGs in education, analyzing state-of-the-art methodologies, and identifying research gaps and limitations, paving the way for future advancements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.) more...

The current management of patients with multimorbidity is suboptimal, with either a single-disease approach to care or treatment guideline adaptations that result in poor adherence due to their complexity. Although this has resulted in calls for more holistic and personalized approaches to prescribing, progress toward these goals has remained slow. With the rapid advancement of machine learning (ML) methods, promising approaches now also exist to accelerate the advance of precision medicine in multimorbidity. These include analyzing disease comorbidity networks, using knowledge graphs that integrate knowledge from different medical domains, and applying network analysis and graph ML. Multimorbidity disease networks have been used to improve disease diagnosis, treatment recommendations, and patient prognosis. Knowledge graphs that combine different medical entities connected by multiple relationship types integrate data from different sources, allowing for complex interactions and creating a continuous flow of information. Network analysis and graph ML can then extract the topology and structure of networks and reveal hidden properties, including disease phenotypes, network hubs, and pathways; predict drugs for repurposing; and determine safe and more holistic treatments. In this article, we describe the basic concepts of creating bipartite and unipartite disease and patient networks and review the use of knowledge graphs, graph algorithms, graph embedding methods, and graph ML within the context of multimorbidity. Specifically, we provide an overview of the application of graph theory for studying multimorbidity, the methods employed to extract knowledge from graphs, and examples of the application of disease networks for determining the structure and pathways of multimorbidity, identifying disease phenotypes, predicting health outcomes, and selecting safe and effective treatments. In today's modern data-hungry, ML-focused world, such network-based techniques are likely to be at the forefront of developing robust clinical decision support tools for safer and more holistic approaches to treating older patients with multimorbidity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Woodman, Koczwara and Mangoni.) more...

Drug discovery is adapting to novel technologies such as data science, informatics, and artificial intelligence (AI) to accelerate effective treatment development while reducing costs and animal experiments. AI is transforming drug discovery, as indicated by increasing interest from investors, industrial and academic scientists, and legislators. Successful drug discovery requires optimizing properties related to pharmacodynamics, pharmacokinetics, and clinical outcomes. This review discusses the use of AI in the three pillars of drug discovery: diseases, targets, and therapeutic modalities, with a focus on small-molecule drugs. AI technologies, such as generative chemistry, machine learning, and multiproperty optimization, have enabled several compounds to enter clinical trials. The scientific community must carefully vet known information to address the reproducibility crisis. The full potential of AI in drug discovery can only be realized with sufficient ground truth and appropriate human intervention at later pipeline stages. more...

Important tasks in biomedical discovery such as predicting gene functions, gene-disease associations, and drug repurposing opportunities are often framed as network edge prediction. The number of edges connecting to a node, termed degree, can vary greatly across nodes in real biomedical networks, and the distribution of degrees varies between networks. If degree strongly influences edge prediction, then imbalance or bias in the distribution of degrees could lead to nonspecific or misleading predictions. We introduce a network permutation framework to quantify the effects of node degree on edge prediction. Our framework decomposes performance into the proportions attributable to degree and the network's specific connections using network permutation to generate features that depend only on degree. We discover that performance attributable to factors other than degree is often only a small portion of overall performance. Researchers seeking to predict new or missing edges in biological networks should use our permutation approach to obtain a baseline for performance that may be nonspecific because of degree. We released our methods as an open-source Python package (https://github.com/hetio/xswap/)., (© The Author(s) 2024. Published by Oxford University Press GigaScience.) more...

Background and Objective: The adoption of new technologies in clinical care systems has propitiated the availability of a great amount of valuable data. However, this data is usually heterogeneous, requiring its harmonization to be integrated and analysed. We propose a semantic-driven harmonization framework that (1) enables the meaningful sharing and integration of healthcare data across institutions and (2) facilitates the analysis and exploitation of the shared data., Methods: The framework includes an ontology-based common data model (i.e. SCDM), a data transformation pipeline and a semantic query system. Heterogeneous datasets, mapped to different terminologies, are integrated by using an ontology-based infrastructure rooted in a top-level ontology. A graph database is generated by using these mappings, and web-based semantic query system facilitates data exploration., Results: Several datasets from different European institutions have been integrated by using the framework in the context of the European H2020 Precise4Q project. Through the query system, data scientists were able to explore data and use it for building machine learning models., Conclusions: The flexible data representation using RDF, together with the formal semantic underpinning provided by the SCDM, have enabled the semantic integration, query and advanced exploitation of heterogeneous data in the context of the Precise4Q project., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.) more...

Teaching scientific literature analysis skills is a critical step in research training. Here I describe a 6-week skill-building module on understanding scientific literature, incorporated into a 10-week undergraduate honors research practice course in Neuroscience. Key pedagogical components include: 1) student-centered active-learning, skill-building and community-building activities; 2) persistent adoption of a proven CREATE method and a novel curate scientific summary (CSS) method for teaching scientific literature analysis skills; 3) collaborative class organization consisting of persistent learning pods (PLPs) to facilitate student-driven participation and peer learning; and, 4) role play of a real research lab. Skill development was assessed using a self-assessment survey (SAS) and longitudinal evaluation of the CREATE and CSS methods application by the PLPs to analyze primary research articles (PRAs) over four weeks. Outcomes demonstrate alleviation of pre-existing student anxiety to read complex scientific literature and advancement of critical-thinking and collaborative skills. Specifically, the SAS responses indicate that student perception about reading scientific literature transformed from being a daunting task to an enjoyable activity; this enhanced their confidence in evaluating scientific literature. PLPs fostered student engagement, peer instruction, and community building, and contributed to skill development. Weekly assessment of CREATE and CSS application highlighted marked improvements in students' abilities to analyze and critique complicated scientific material. Role playing a research lab setting with a focused research theme facilitated integrative understanding of a frontier topic in Neuroscience. The outlined innovative approach can be adopted in Course-based Undergraduate Research Experience (CURE) and should help contribute to systematizing didactic practices to train neuroscientists., (Copyright © 2023 Faculty for Undergraduate Neuroscience.) more...

Chronic low back pain (LBP) is influenced by a broad spectrum of patient-specific factors as codified in domains of the biopsychosocial model (BSM). Operationalizing the BSM into research and clinical care is challenging because most investigators work in silos that concentrate on only one or two BSM domains. Furthermore, the expanding, multidisciplinary nature of BSM research creates practical limitations as to how individual investigators integrate current data into their processes of generating impactful hypotheses. The rapidly advancing field of artificial intelligence (AI) is providing new tools for organizing knowledge, but the practical aspects for how AI may advance LBP research and clinical are beginning to be explored. The goals of the work presented here are to: (1) explore the current capabilities of knowledge integration technologies (large language models (LLM), similarity graphs (SGs), and knowledge graphs (KGs)) to synthesize biomedical literature and depict multimodal relationships reflected in the BSM, and; (2) highlight limitations, implementation details, and future areas of research to improve performance. We demonstrate preliminary evidence that LLMs, like GPT-3, may be useful in helping scientists analyze and distinguish cLBP publications across multiple BSM domains and determine the degree to which the literature supports or contradicts emergent hypotheses. We show that SG representations and KGs enable exploring LBP's literature in novel ways, possibly providing, trans-disciplinary perspectives or insights that are currently difficult, if not infeasible to achieve. The SG approach is automated, simple, and inexpensive to execute, and thereby may be useful for early-phase literature and narrative explorations beyond one's areas of expertise. Likewise, we show that KGs can be constructed using automated pipelines, queried to provide semantic information, and analyzed to explore trans-domain linkages. The examples presented support the feasibility for LBP-tailored AI protocols to organize knowledge and support developing and refining trans-domain hypotheses., Competing Interests: The authors have no conflict of interest., (© 2023 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.) more...

Finding patterns among risk factors and chronic illness can suggest similar causes, provide guidance to improve healthy lifestyles, and give clues for possible treatments for outliers. Prior studies have typically isolated data challenges from single-disease datasets. However, the predictive power of multiple diseases is more helpful in establishing a healthy lifestyle than investigating one disease. Most studies typically focus on single-disease datasets; however, to ensure that health advice is generalized and contemporary, the features that predict the likelihood of many diseases can improve health advice effectiveness when considering the patient's point of view. We construct and present a novel knowledge-based qualitative method to remove redundant features from a dataset and redefine the outliers. The results of our trials upon five annual chronic disease health surveys demonstrate that our Knowledge Graph-based feature selection, when applied to many machine learning and deep learning multi-label classifiers, can improve classification performance. Our methodology is compatible with future directions, such as graph neural networks. It provides clinicians with an efficient process to select the most relevant health survey questions and responses regarding single or many human organ systems., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.) more...