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1.
BMC Bioinformatics ; 25(1): 62, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326757

RESUMEN

BACKGROUND: Recent developments in the domain of biomedical knowledge bases (KBs) open up new ways to exploit biomedical knowledge that is available in the form of KBs. Significant work has been done in the direction of biomedical KB creation and KB completion, specifically, those having gene-disease associations and other related entities. However, the use of such biomedical KBs in combination with patients' temporal clinical data still largely remains unexplored, but has the potential to immensely benefit medical diagnostic decision support systems. RESULTS: We propose two new algorithms, LOADDx and SCADDx, to combine a patient's gene expression data with gene-disease association and other related information available in the form of a KB, to assist personalized disease diagnosis. We have tested both of the algorithms on two KBs and on four real-world gene expression datasets of respiratory viral infection caused by Influenza-like viruses of 19 subtypes. We also compare the performance of proposed algorithms with that of five existing state-of-the-art machine learning algorithms (k-NN, Random Forest, XGBoost, Linear SVM, and SVM with RBF Kernel) using two validation approaches: LOOCV and a single internal validation set. Both SCADDx and LOADDx outperform the existing algorithms when evaluated with both validation approaches. SCADDx is able to detect infections with up to 100% accuracy in the cases of Datasets 2 and 3. Overall, SCADDx and LOADDx are able to detect an infection within 72 h of infection with 91.38% and 92.66% average accuracy respectively considering all four datasets, whereas XGBoost, which performed best among the existing machine learning algorithms, can detect the infection with only 86.43% accuracy on an average. CONCLUSIONS: We demonstrate how our novel idea of using the most and least differentially expressed genes in combination with a KB can enable identification of the diseases that a patient is most likely to have at a particular time, from a KB with thousands of diseases. Moreover, the proposed algorithms can provide a short ranked list of the most likely diseases for each patient along with their most affected genes, and other entities linked with them in the KB, which can support health care professionals in their decision-making.


Asunto(s)
Bases del Conocimiento , Transcriptoma , Humanos , Algoritmos , Aprendizaje Automático
2.
J Proteome Res ; 23(2): 532-549, 2024 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-38232391

RESUMEN

Since 2010, the Human Proteome Project (HPP), the flagship initiative of the Human Proteome Organization (HUPO), has pursued two goals: (1) to credibly identify the protein parts list and (2) to make proteomics an integral part of multiomics studies of human health and disease. The HPP relies on international collaboration, data sharing, standardized reanalysis of MS data sets by PeptideAtlas and MassIVE-KB using HPP Guidelines for quality assurance, integration and curation of MS and non-MS protein data by neXtProt, plus extensive use of antibody profiling carried out by the Human Protein Atlas. According to the neXtProt release 2023-04-18, protein expression has now been credibly detected (PE1) for 18,397 of the 19,778 neXtProt predicted proteins coded in the human genome (93%). Of these PE1 proteins, 17,453 were detected with mass spectrometry (MS) in accordance with HPP Guidelines and 944 by a variety of non-MS methods. The number of neXtProt PE2, PE3, and PE4 missing proteins now stands at 1381. Achieving the unambiguous identification of 93% of predicted proteins encoded from across all chromosomes represents remarkable experimental progress on the Human Proteome parts list. Meanwhile, there are several categories of predicted proteins that have proved resistant to detection regardless of protein-based methods used. Additionally there are some PE1-4 proteins that probably should be reclassified to PE5, specifically 21 LINC entries and ∼30 HERV entries; these are being addressed in the present year. Applying proteomics in a wide array of biological and clinical studies ensures integration with other omics platforms as reported by the Biology and Disease-driven HPP teams and the antibody and pathology resource pillars. Current progress has positioned the HPP to transition to its Grand Challenge Project focused on determining the primary function(s) of every protein itself and in networks and pathways within the context of human health and disease.


Asunto(s)
Anticuerpos , Proteoma , Humanos , Proteoma/genética , Proteoma/análisis , Bases de Datos de Proteínas , Espectrometría de Masas/métodos , Proteómica/métodos
3.
Brief Bioinform ; 23(5)2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36058206

RESUMEN

Updated and expert-quality knowledge bases are fundamental to biomedical research. A knowledge base established with human participation and subject to multiple inspections is needed to support clinical decision making, especially in the growing field of precision oncology. The number of original publications in this field has risen dramatically with the advances in technology and the evolution of in-depth research. Consequently, the issue of how to gather and mine these articles accurately and efficiently now requires close consideration. In this study, we present OncoPubMiner (https://oncopubminer.chosenmedinfo.com), a free and powerful system that combines text mining, data structure customisation, publication search with online reading and project-centred and team-based data collection to form a one-stop 'keyword in-knowledge out' oncology publication mining platform. The platform was constructed by integrating all open-access abstracts from PubMed and full-text articles from PubMed Central, and it is updated daily. OncoPubMiner makes obtaining precision oncology knowledge from scientific articles straightforward and will assist researchers in efficiently developing structured knowledge base systems and bring us closer to achieving precision oncology goals.


Asunto(s)
Neoplasias , Minería de Datos , Humanos , Oncología Médica , Medicina de Precisión , PubMed , Publicaciones
4.
J Med Internet Res ; 26: e46777, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38635981

RESUMEN

BACKGROUND: As global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease's etiology and response to drugs. OBJECTIVE: We designed the Alzheimer's Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics. METHODS: We designed the AlzKB as a large, heterogeneous graph knowledge base assembled using 22 diverse external data sources describing biological and pharmaceutical entities at different levels of organization (eg, chemicals, genes, anatomy, and diseases). AlzKB uses a Web Ontology Language 2 ontology to enforce semantic consistency and allow for ontological inference. We provide a public version of AlzKB and allow users to run and modify local versions of the knowledge base. RESULTS: AlzKB is freely available on the web and currently contains 118,902 entities with 1,309,527 relationships between those entities. To demonstrate its value, we used graph data science and machine learning to (1) propose new therapeutic targets based on similarities of AD to Parkinson disease and (2) repurpose existing drugs that may treat AD. For each use case, AlzKB recovers known therapeutic associations while proposing biologically plausible new ones. CONCLUSIONS: AlzKB is a new, publicly available knowledge resource that enables researchers to discover complex translational associations for AD drug discovery. Through 2 use cases, we show that it is a valuable tool for proposing novel therapeutic hypotheses based on public biomedical knowledge.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Reconocimiento de Normas Patrones Automatizadas , Bases del Conocimiento , Aprendizaje Automático , Conocimiento
5.
J Med Internet Res ; 26: e54737, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283665

RESUMEN

BACKGROUND: Despite the emerging application of clinical decision support systems (CDSS) in pregnancy care and the proliferation of artificial intelligence (AI) over the last decade, it remains understudied regarding the role of AI in CDSS specialized for pregnancy care. OBJECTIVE: To identify and synthesize AI-augmented CDSS in pregnancy care, CDSS functionality, AI methodologies, and clinical implementation, we reported a systematic review based on empirical studies that examined AI-augmented CDSS in pregnancy care. METHODS: We retrieved studies that examined AI-augmented CDSS in pregnancy care using database queries involved with titles, abstracts, keywords, and MeSH (Medical Subject Headings) terms. Bibliographic records from their inception to 2022 were retrieved from PubMed/MEDLINE (n=206), Embase (n=101), and ACM Digital Library (n=377), followed by eligibility screening and literature review. The eligibility criteria include empirical studies that (1) developed or tested AI methods, (2) developed or tested CDSS or CDSS components, and (3) focused on pregnancy care. Data of studies used for review and appraisal include title, abstract, keywords, MeSH terms, full text, and supplements. Publications with ancillary information or overlapping outcomes were synthesized as one single study. Reviewers independently reviewed and assessed the quality of selected studies. RESULTS: We identified 30 distinct studies of 684 studies from their inception to 2022. Topics of clinical applications covered AI-augmented CDSS from prenatal, early pregnancy, obstetric care, and postpartum care. Topics of CDSS functions include diagnostic support, clinical prediction, therapeutics recommendation, and knowledge base. CONCLUSIONS: Our review acknowledged recent advances in CDSS studies including early diagnosis of prenatal abnormalities, cost-effective surveillance, prenatal ultrasound support, and ontology development. To recommend future directions, we also noted key gaps from existing studies, including (1) decision support in current childbirth deliveries without using observational data from consequential fetal or maternal outcomes in future pregnancies; (2) scarcity of studies in identifying several high-profile biases from CDSS, including social determinants of health highlighted by the American College of Obstetricians and Gynecologists; and (3) chasm between internally validated CDSS models, external validity, and clinical implementation.


Asunto(s)
Inteligencia Artificial , Sistemas de Apoyo a Decisiones Clínicas , Humanos , Embarazo , Femenino , Atención Prenatal/métodos
6.
BMC Med Inform Decis Mak ; 24(1): 216, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085883

RESUMEN

BACKGROUND: Intraoperative neurophysiological monitoring (IOM) plays a pivotal role in enhancing patient safety during neurosurgical procedures. This vital technique involves the continuous measurement of evoked potentials to provide early warnings and ensure the preservation of critical neural structures. One of the primary challenges has been the effective documentation of IOM events with semantically enriched characterizations. This study aimed to address this challenge by developing an ontology-based tool. METHODS: We structured the development of the IOM Documentation Ontology (IOMDO) and the associated tool into three distinct phases. The initial phase focused on the ontology's creation, drawing from the OBO (Open Biological and Biomedical Ontology) principles. The subsequent phase involved agile software development, a flexible approach to encapsulate the diverse requirements and swiftly produce a prototype. The last phase entailed practical evaluation within real-world documentation settings. This crucial stage enabled us to gather firsthand insights, assessing the tool's functionality and efficacy. The observations made during this phase formed the basis for essential adjustments to ensure the tool's productive utilization. RESULTS: The core entities of the ontology revolve around central aspects of IOM, including measurements characterized by timestamp, type, values, and location. Concepts and terms of several ontologies were integrated into IOMDO, e.g., the Foundation Model of Anatomy (FMA), the Human Phenotype Ontology (HPO) and the ontology for surgical process models (OntoSPM) related to general surgical terms. The software tool developed for extending the ontology and the associated knowledge base was built with JavaFX for the user-friendly frontend and Apache Jena for the robust backend. The tool's evaluation involved test users who unanimously found the interface accessible and usable, even for those without extensive technical expertise. CONCLUSIONS: Through the establishment of a structured and standardized framework for characterizing IOM events, our ontology-based tool holds the potential to enhance the quality of documentation, benefiting patient care by improving the foundation for informed decision-making. Furthermore, researchers can leverage the semantically enriched data to identify trends, patterns, and areas for surgical practice enhancement. To optimize documentation through ontology-based approaches, it's crucial to address potential modeling issues that are associated with the Ontology of Adverse Events.


Asunto(s)
Ontologías Biológicas , Procedimientos Neuroquirúrgicos , Humanos , Procedimientos Neuroquirúrgicos/normas , Documentación/normas , Programas Informáticos
7.
Alzheimers Dement ; 20(2): 1123-1136, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37881831

RESUMEN

INTRODUCTION: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site Alzheimer's Genomics Database (GenomicsDB) is a public knowledge base of Alzheimer's disease (AD) genetic datasets and genomic annotations. METHODS: GenomicsDB uses a custom systems architecture to adopt and enforce rigorous standards that facilitate harmonization of AD-relevant genome-wide association study summary statistics datasets with functional annotations, including over 230 million annotated variants from the AD Sequencing Project. RESULTS: GenomicsDB generates interactive reports compiled from the harmonized datasets and annotations. These reports contextualize AD-risk associations in a broader functional genomic setting and summarize them in the context of functionally annotated genes and variants. DISCUSSION: Created to make AD-genetics knowledge more accessible to AD researchers, the GenomicsDB is designed to guide users unfamiliar with genetic data in not only exploring but also interpreting this ever-growing volume of data. Scalable and interoperable with other genomics resources using data technology standards, the GenomicsDB can serve as a central hub for research and data analysis on AD and related dementias. HIGHLIGHTS: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) offers to the public a unique, disease-centric collection of AD-relevant GWAS summary statistics datasets. Interpreting these data is challenging and requires significant bioinformatics expertise to standardize datasets and harmonize them with functional annotations on genome-wide scales. The NIAGADS Alzheimer's GenomicsDB helps overcome these challenges by providing a user-friendly public knowledge base for AD-relevant genetics that shares harmonized, annotated summary statistics datasets from the NIAGADS repository in an interpretable, easily searchable format.


Asunto(s)
Enfermedad de Alzheimer , Estados Unidos , Humanos , Enfermedad de Alzheimer/genética , Estudio de Asociación del Genoma Completo , National Institute on Aging (U.S.) , Genómica , Bases de Datos Factuales , Predisposición Genética a la Enfermedad/genética
8.
Brief Bioinform ; 22(3)2021 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-32572450

RESUMEN

Fibrosis is a key component in the pathogenic mechanism of a variety of diseases. These diseases involving fibrosis may share common mechanisms and therapeutic targets, and therefore common intervention strategies and medicines may be applicable for these diseases. For this reason, deliberately introducing anti-fibrosis characteristics into predictive modeling may lead to more success in drug repositioning. In this study, anti-fibrosis knowledge base was first built by collecting data from multiple resources. Both structural and biological profiles were then derived from the knowledge base and used for constructing machine learning models including Structural Profile Prediction Model (SPPM) and Biological Profile Prediction Model (BPPM). Three external public data sets were employed for validation purpose and further exploration of potential repositioning drugs in wider chemical space. The resulting SPPM and BPPM models achieve area under the receiver operating characteristic curve (area under the curve) of 0.879 and 0.972 in the training set, and 0.814 and 0.874 in the testing set. Additionally, our results also demonstrate that substantial amount of multi-targeting natural products possess notable anti-fibrosis characteristics and might serve as encouraging candidates in fibrosis treatment and drug repositioning. To leverage our methodology and findings, we developed repositioning prediction platform, drug repositioning based on anti-fibrosis characteristic that is freely accessible via https://www.biosino.org/drafc.


Asunto(s)
Biología Computacional , Bases de Datos Factuales , Reposicionamiento de Medicamentos , Aprendizaje Automático , Modelos Biológicos , Fibrosis , Humanos
9.
NMR Biomed ; 36(4): e4853, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36264537

RESUMEN

There are about 1500 genetic metabolic diseases. A small number of treatable diseases are diagnosed by newborn screening programs, which are continually being developed. However, most diseases can only be diagnosed based on clinical symptoms or metabolic findings. The main biological fluids used are urine, plasma and, in special situations, cerebrospinal fluid. In contrast to commonly used methods such as gas chromatography and high performance liquid chromatography mass spectrometry, ex vivo proton spectroscopy (1 H-NMR) is not yet used in routine clinical practice, although it has been recommended for more than 30 years. Automatic analysis and improved NMR technology have also expanded the applications used for the diagnosis of inborn errors of metabolism. We provide a mini-overview of typical applications, especially in urine but also in plasma, used to diagnose common but also rare genetic metabolic diseases with 1 H-NMR. The use of computer-assisted diagnostic suggestions can facilitate interpretation of the profiles. In a proof of principle, to date, 182 reports of 59 different diseases and 500 reports of healthy children are stored. The percentage of correct automatic diagnoses was 74%. Using the same 1 H-NMR profile-targeted analysis, it is possible to apply an untargeted approach that distinguishes profile differences from healthy individuals. Thus, additional conditions such as lysosomal storage diseases or drug interferences are detectable. Furthermore, because 1 H-NMR is highly reproducible and can detect a variety of different substance categories, the metabolomic approach is suitable for monitoring patient treatment and revealing additional factors such as nutrition and microbiome metabolism. Besides the progress in analytical techniques, a multiomics approach is most effective to combine metabolomics with, for example, whole exome sequencing, to also diagnose patients with nondetectable metabolic abnormalities in biological fluids. In this mini review we also provide our own data to demonstrate the role of NMR in a multiomics platform in the field of inborn errors of metabolism.


Asunto(s)
Errores Innatos del Metabolismo , Niño , Recién Nacido , Humanos , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/metabolismo , Protones , Cromatografía de Gases y Espectrometría de Masas , Espectroscopía de Resonancia Magnética , Computadores
10.
J Biomed Inform ; 142: 104383, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37196989

RESUMEN

OBJECTIVE: To demonstrate and develop an approach enabling individual researchers or small teams to create their own ad-hoc, lightweight knowledge bases tailored for specialized scientific interests, using text-mining over scientific literature, and demonstrate the effectiveness of these knowledge bases in hypothesis generation and literature-based discovery (LBD). METHODS: We propose a lightweight process using an extractive search framework to create ad-hoc knowledge bases, which require minimal training and no background in bio-curation or computer science. These knowledge bases are particularly effective for LBD and hypothesis generation using Swanson's ABC method. The personalized nature of the knowledge bases allows for a somewhat higher level of noise than "public facing" ones, as researchers are expected to have prior domain experience to separate signal from noise. Fact verification is shifted from exhaustive verification of the knowledge base to post-hoc verification of specific entries of interest, allowing researchers to assess the correctness of relevant knowledge base entries by considering the paragraphs in which the facts were introduced. RESULTS: We demonstrate the methodology by constructing several knowledge bases of different kinds: three knowledge bases that support lab-internal hypothesis generation: Drug Delivery to Ovarian Tumors (DDOT); Tissue Engineering and Regeneration; Challenges in Cancer Research; and an additional comprehensive, accurate knowledge base designated as a public resource for the wider community on the topic of Cell Specific Drug Delivery (CSDD). In each case, we show the design and construction process, along with relevant visualizations for data exploration, and hypothesis generation. For CSDD and DDOT we also show meta-analysis, human evaluation, and in vitro experimental evaluation. CONCLUSION: Our approach enables researchers to create personalized, lightweight knowledge bases for specialized scientific interests, effectively facilitating hypothesis generation and literature-based discovery (LBD). By shifting fact verification efforts to post-hoc verification of specific entries, researchers can focus on exploring and generating hypotheses based on their expertise. The constructed knowledge bases demonstrate the versatility and adaptability of our approach to versatile research interests. The web-based platform, available at https://spike-kbc.apps.allenai.org, provides researchers with a valuable tool for rapid construction of knowledge bases tailored to their needs.


Asunto(s)
Minería de Datos , Descubrimiento del Conocimiento , Humanos , Minería de Datos/métodos , Descubrimiento del Conocimiento/métodos , Publicaciones
11.
J Biomed Inform ; 143: 104405, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37270143

RESUMEN

BACKGROUND: Scientific discovery progresses by exploring new and uncharted territory. More specifically, it advances by a process of transforming unknown unknowns first into known unknowns, and then into knowns. Over the last few decades, researchers have developed many knowledge bases to capture and connect the knowns, which has enabled topic exploration and contextualization of experimental results. But recognizing the unknowns is also critical for finding the most pertinent questions and their answers. Prior work on known unknowns has sought to understand them, annotate them, and automate their identification. However, no knowledge-bases yet exist to capture these unknowns, and little work has focused on how scientists might use them to trace a given topic or experimental result in search of open questions and new avenues for exploration. We show here that a knowledge base of unknowns can be connected to ontologically grounded biomedical knowledge to accelerate research in the field of prenatal nutrition. RESULTS: We present the first ignorance-base, a knowledge-base created by combining classifiers to recognize ignorance statements (statements of missing or incomplete knowledge that imply a goal for knowledge) and biomedical concepts over the prenatal nutrition literature. This knowledge-base places biomedical concepts mentioned in the literature in context with the ignorance statements authors have made about them. Using our system, researchers interested in the topic of vitamin D and prenatal health were able to uncover three new avenues for exploration (immune system, respiratory system, and brain development) by searching for concepts enriched in ignorance statements. These were buried among the many standard enriched concepts. Additionally, we used the ignorance-base to enrich concepts connected to a gene list associated with vitamin D and spontaneous preterm birth and found an emerging topic of study (brain development) in an implied field (neuroscience). The researchers could look to the field of neuroscience for potential answers to the ignorance statements. CONCLUSION: Our goal is to help students, researchers, funders, and publishers better understand the state of our collective scientific ignorance (known unknowns) in order to help accelerate research through the continued illumination of and focus on the known unknowns and their respective goals for scientific knowledge.


Asunto(s)
Bases del Conocimiento , Conocimiento , Procesamiento de Lenguaje Natural , Femenino , Humanos , Recién Nacido , Nacimiento Prematuro , Publicaciones , Vitamina D
12.
J Med Internet Res ; 25: e45364, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38090790

RESUMEN

Most mobile health (mHealth) decision support systems currently available for chronic obstructive respiratory diseases (CORDs) are not supported by clinical evidence or lack clinical validation. The development of the knowledge base that will feed the clinical decision support system is a crucial step that involves the collection and systematization of clinical knowledge from relevant scientific sources and its representation in a human-understandable and computer-interpretable way. This work describes the development and initial validation of a clinical knowledge base that can be integrated into mHealth decision support systems developed for patients with CORDs. A multidisciplinary team of health care professionals with clinical experience in respiratory diseases, together with data science and IT professionals, defined a new framework that can be used in other evidence-based systems. The knowledge base development began with a thorough review of the relevant scientific sources (eg, disease guidelines) to identify the recommendations to be implemented in the decision support system based on a consensus process. Recommendations were selected according to predefined inclusion criteria: (1) applicable to individuals with CORDs or to prevent CORDs, (2) directed toward patient self-management, (3) targeting adults, and (4) within the scope of the knowledge domains and subdomains defined. Then, the selected recommendations were prioritized according to (1) a harmonized level of evidence (reconciled from different sources); (2) the scope of the source document (international was preferred); (3) the entity that issued the source document; (4) the operability of the recommendation; and (5) health care professionals' perceptions of the relevance, potential impact, and reach of the recommendation. A total of 358 recommendations were selected. Next, the variables required to trigger those recommendations were defined (n=116) and operationalized into logical rules using Boolean logical operators (n=405). Finally, the knowledge base was implemented in an intelligent individualized coaching component and pretested with an asthma use case. Initial validation of the knowledge base was conducted internally using data from a population-based observational study of individuals with or without asthma or rhinitis. External validation of the appropriateness of the recommendations with the highest priority level was conducted independently by 4 physicians. In addition, a strategy for knowledge base updates, including an easy-to-use rules editor, was defined. Using this process, based on consensus and iterative improvement, we developed and conducted preliminary validation of a clinical knowledge base for CORDs that translates disease guidelines into personalized patient recommendations. The knowledge base can be used as part of mHealth decision support systems. This process could be replicated in other clinical areas.


Asunto(s)
Asma , Sistemas de Apoyo a Decisiones Clínicas , Enfermedades Respiratorias , Telemedicina , Adulto , Humanos , Consenso , Personal de Salud , Asma/terapia
13.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37686360

RESUMEN

Coronavirus disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a "cytokine storm", and neuroinflammation. COVID-19's upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy bodies made primarily of the α-synuclein protein encoded by the synuclein alpha (SNCA) gene. We hypothesize that COVID-19 may modulate PD progression through neuroinflammation induced by cytokine storms. This study aimed to elucidate the possible mechanisms and signaling pathways involved in COVID-19-triggered pathology associated with neurodegenerative diseases like PD. This study presents the analysis of the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN's Ingenuity Pathway Analysis (IPA), the study identified the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.


Asunto(s)
COVID-19 , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enzima Convertidora de Angiotensina 2/genética , Enfermedades Neuroinflamatorias , SARS-CoV-2 , Síndrome de Liberación de Citoquinas , Interferón gamma
14.
Appl Intell (Dordr) ; 53(5): 5179-5198, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35756085

RESUMEN

Recently, an exciting experimental conclusion in Li et al. (Knowl Inf Syst 62(2):611-637, 1) about measures of uncertainty for knowledge bases has attracted great research interest for many scholars. However, these efforts lack solid theoretical interpretations for the experimental conclusion. The main limitation of their research is that the final experimental conclusions are only derived from experiments on three datasets, which makes it still unknown whether the conclusion is universal. In our work, we first review the mathematical theories, definitions, and tools for measuring the uncertainty of knowledge bases. Then, we provide a series of rigorous theoretical proofs to reveal the reasons for the superiority of using the knowledge amount of knowledge structure to measure the uncertainty of the knowledge bases. Combining with experiment results, we verify that knowledge amount has much better performance for measuring uncertainty of knowledge bases. Hence, we prove an empirical conclusion established through experiments from a mathematical point of view. In addition, we find that for some knowledge bases that cannot be classified by entity attributes, such as ProBase (a probabilistic taxonomy), our conclusion is still applicable. Therefore, our conclusions have a certain degree of universality and interpretability and provide a theoretical basis for measuring the uncertainty of many different types of knowledge bases, and the findings of this study have a number of important implications for future practice.

15.
BMC Public Health ; 22(1): 2325, 2022 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-36510181

RESUMEN

BACKGROUND: Despite effectiveness of action and coping planning in digital health interventions to promote physical activity (PA), attrition rates remain high. Indeed, support to make plans is often abstract and similar for each individual. Nevertheless, people are different, and context varies. Tailored support at the content level, involving suggestions of specific plans that are personalized to the individual, may reduce attrition and improve outcomes in digital health interventions. The aim of this study was to investigate whether user information relates toward specific action and coping plans using a clustering method. In doing so, we demonstrate how knowledge can be acquired in order to develop a knowledge-base, which might provide personalized suggestions in a later phase. METHODS: To establish proof-of-concept for this approach, data of 65 healthy adults, including 222 action plans and 204 coping plans, were used and were collected as part of the digital health intervention MyPlan 2.0 to promote PA. As a first step, clusters of action plans, clusters of coping plans and clusters of combinations of action plans and barriers of coping plans were identified using hierarchical clustering. As a second step, relations with user information (i.e. gender, motivational stage, ...) were examined using anova's and chi2-tests. RESULTS: First, three clusters of action plans, eight clusters of coping plans and eight clusters of the combination of action and coping plans were identified. Second, relating these clusters to user information was possible for action plans: 1) Users with a higher BMI related more to outdoor leisure activities (F = 13.40, P < .001), 2) Women, users that didn't perform PA regularly yet, or users with a job related more to household activities (X2 = 16.92, P < .001; X2 = 20.34, P < .001; X2 = 10.79, P = .004; respectively), 3) Younger users related more to active transport and different sports activities (F = 14.40, P < .001). However, relating clusters to user information proved difficult for the coping plans and combination of action and coping plans. CONCLUSIONS: The approach used in this study might be a feasible approach to acquire input for a knowledge-base, however more data (i.e. contextual and dynamic user information) from possible end users should be acquired in future research. This might result in a first type of context-aware personalized suggestions on the content level. TRIAL REGISTRATION: The digital health intervention MyPlan 2.0 was preregistered as a clinical trial (ID:NCT03274271). Release date: 6-September-2017.


Asunto(s)
Ejercicio Físico , Actividades Recreativas , Adulto , Humanos , Femenino , Adaptación Psicológica , Motivación
16.
BMC Med Inform Decis Mak ; 21(Suppl 11): 369, 2022 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-36419042

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease with different responses to targeted therapies due to various factors, and the treatment effect differs significantly between individuals. Personalize medical treatment (PMT) is a method that takes individual patient characteristics into consideration, making it the most effective way to deal with this issue. Patient similarity and clustering analysis is an important aspect of PMT. This paper describes how to build a knowledge base using formal concept analysis (FCA), which clusters patients based on their similarity and preserves the relations between clusters in hierarchical structural form. METHODS: Prognostic factors (attributes) of 2442 CRC patients, including patient age, cancer cell differentiation, lymphatic invasion and metastasis stages were used to build a formal context in FCA. A concept was defined as a set of patients with their shared attributes. The formal context was formed based on the similarity scores between each concept identified from the dataset, which can be used as a knowledge base. RESULTS: A hierarchical knowledge base was constructed along with the clinical records of the diagnosed CRC patients. For each new patient, a similarity score to each existing concept in the knowledge base can be retrieved with different similarity calculations. The ranked similarity scores that are associated with the concepts can offer references for treatment plans. CONCLUSIONS: Patients that share the same concept indicates the potential similar effect from same clinical procedures or treatments. In conjunction with a clinician's ability to undergo flexible analyses and apply appropriate judgement, the knowledge base allows faster and more effective decisions to be made for patient treatment and care.


Asunto(s)
Neoplasias Colorrectales , Atención al Paciente , Humanos , Bases del Conocimiento , Análisis por Conglomerados , Juicio , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia
17.
Sensors (Basel) ; 22(20)2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36298104

RESUMEN

Aiming at the problems of single detection target of existing distributed denial of service (DDoS) attacks, incomplete detection datasets and privacy caused by shared datasets, we propose a trusted multi-domain DDoS detection method based on federated learning. Firstly, we divide the types of DDoS attacks into different sub-attacks, design the federated learning dataset for DDoS detection in each domain, and use them to realize a more comprehensive detection method of DDoS attacks on the premise of protecting the data privacy of each domain. Secondly, in order to improve the robustness of federated learning and alleviate poisoning attack, we propose a reputation evaluation method based on blockchain, which estimates interaction reputation, data reputation and resource reputation of each participant comprehensively, so as to obtain the trusted federated learning participants and identify the malicious participants. In addition, we also propose a combination scheme of multi-domain detection and distributed knowledge base and design a feature graph of malicious behavior based on a knowledge graph to realize the memory of multi-domain feature knowledge. The experimental results show that the accuracy of most categories of the multi-domain DDoS detection method can reach more than 95% with the protection of datasets, and the reputation evaluation method proposed in this paper has a higher ability to identify malicious participants against the data poisoning attack when the threshold is set to 0.6.


Asunto(s)
Aprendizaje , Privacidad , Humanos , Aprendizaje Automático
18.
Sensors (Basel) ; 22(22)2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36433613

RESUMEN

In view of various security requirements, there are various security services in the network. In particular, DDoS attacks have various types and detection methods. How to flexibly combine security services and make full use of the information provided by security services have become urgent problems to be solved. This paper combines the reasoning ability of the malicious behavior knowledge base to realize the dynamic deployment of the service function chain and dynamic configuration of the security service function. The method feeds back the information generated by the security service to the knowledge base. After the analysis of the knowledge base, the service function chain path and the security service configuration policies are generated, and these policies will be dynamically distributed to the security service function. Finally, security services can be dynamically arranged for different network traffic, realizing the coordinated use of various security services and improving the overall detection rate of the network. The experimental results show that by arranging the paths under the UDP and the TCP, the overall detection rate of the network can reach 99% and 88%, respectively, indicating that it has a good overall detection performance for multiple distributed denial of service (DDoS) attacks.


Asunto(s)
Seguridad Computacional , Bases del Conocimiento
19.
Sensors (Basel) ; 22(4)2022 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-35214484

RESUMEN

Collaborative reasoning for knowledge-based visual question answering is challenging but vital and efficient in understanding the features of the images and questions. While previous methods jointly fuse all kinds of features by attention mechanism or use handcrafted rules to generate a layout for performing compositional reasoning, which lacks the process of visual reasoning and introduces a large number of parameters for predicting the correct answer. For conducting visual reasoning on all kinds of image-question pairs, in this paper, we propose a novel reasoning model of a question-guided tree structure with a knowledge base (QGTSKB) for addressing these problems. In addition, our model consists of four neural module networks: the attention model that locates attended regions based on the image features and question embeddings by attention mechanism, the gated reasoning model that forgets and updates the fused features, the fusion reasoning model that mines high-level semantics of the attended visual features and knowledge base and knowledge-based fact model that makes up for the lack of visual and textual information with external knowledge. Therefore, our model performs visual analysis and reasoning based on tree structures, knowledge base and four neural module networks. Experimental results show that our model achieves superior performance over existing methods on the VQA v2.0 and CLVER dataset, and visual reasoning experiments prove the interpretability of the model.


Asunto(s)
Bases del Conocimiento , Redes Neurales de la Computación , Aprendizaje , Solución de Problemas , Semántica
20.
Entropy (Basel) ; 24(12)2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36554210

RESUMEN

In the process of bridge management, large amounts of domain information are accumulated, such as basic attributes, structural defects, technical conditions, etc. However, the valuable information is not fully utilized, resulting in insufficient knowledge service in the field of bridge management. To tackle these problems, this paper proposes a complex knowledge base question answering (C-KBQA) framework for intelligent bridge management based on multi-task learning (MTL) and cross-task constraints (CTC). First, with C-KBQA as the main task, part-of-speech (POS) tagging, topic entity extraction (TEE), and question classification (QC) as auxiliary tasks, an MTL framework is built by sharing encoders and parameters, thereby effectively avoiding the error propagation problem of the pipeline model. Second, cross-task semantic constraints are provided for different subtasks via POS embeddings, entity embeddings, and question-type embeddings. Finally, using template matching, relevant query statements are generated and interaction with the knowledge base is established. The experimental results show that the proposed model outperforms compared mainstream models in terms of TEE and QC on bridge management datasets, and its performance in C-KBQA is outstanding.

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