212 research outputs found

    VO: Vaccine Ontology

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    Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO, "http://www.violinet.org/vaccineontology":http://www.violinet.org/vaccineontology) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented.
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    A diagnostic autoantibody signature for primary cutaneous melanoma

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    Melanoma is an aggressive form of skin cancer that is curable by surgical excision in the majority of cases, if detected at an early stage. To improve early stage melanoma detection, the development of a highly sensitive diagnostic test is of utmost importance. Here we aimed to identify antibodies to a panel of tumour associated antigens that can differentiate primary melanoma patients and healthy individuals. A total of 245 sera from primary melanoma patients and healthy volunteers were screened against a high-throughput microarray platform containing 1627 functional proteins. Following rigorous statistical analysis, we identified a combination of 10 autoantibody biomarkers that, as a panel, displays a sensitivity of 79%, specificity of 84% and an AUC of 0.828 for primary melanoma detection. This melanoma autoantibody signature may prove valuable for the development of a diagnostic blood test for routine population screening that, when used in conjunction with current melanoma diagnostic techniques, could improve the early diagnosis of this malignancy and ultimately decrease the mortality rate of patients

    Evaluating actions to improve air quality at University Hospitals Birmingham NHS Foundation Trust

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    Air pollution is the single largest environmental risk to human health in the UK, exerting a major healthcare sector burden and exacerbating health and social inequalities. The NHS Long Term Plan commits the healthcare sector to reducing emissions from all sources, however, to date few Acute NHS Trusts have implemented air quality focused sustainability plans. In this case study, we assess potential air quality improvement actions at University Hospitals Birmingham NHS Foundation Trust’s, Queen Elizabeth Hospital in Birmingham, UK as a test case for NHS sustainability actions. We generate an evidenced based, prioritized shortlist of actions to mitigate emissions and protect patients, staff, and local communities from air pollution exposure. The project supports adoption of an evidence-based, contextually relevant, approach to air quality management within healthcare provision. The methodology used could be employed by organizations with similar goals to address environmental concerns. View Full-Tex

    VO: Vaccine Ontology

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    The collaborative, community-based Vaccine Ontology (VO) was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Currently VO covers a variety of aspects of the vaccine domain, with an emphasis on classification of vaccines and vaccine components, and on host immune response to vaccines. VO can be used for a number of applications, e.g., ontology-based vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI)

    LRRK2 secretion in exosomes is regulated by 14-3-3

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    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset Parkinson's disease (PD). Emerging evidence suggests a role for LRRK2 in the endocytic pathway. Here, we show that LRRK2 is released in extracellular microvesicles (i.e. exosomes) from cells that natively express LRRK2. LRRK2 localizes to collecting duct epithelial cells in the kidney that actively secrete exosomes into urine. Purified urinary exosomes contain LRRK2 protein that is both dimerized and phosphorylated. We provide a quantitative proteomic profile of 1673 proteins in urinary exosomes and find that known LRRK2 interactors including 14-3-3 are some of the most abundant exosome proteins. Disruption of the 14-3-3 LRRK2 interaction with a 14-3-3 inhibitor or through acute LRRK2 kinase inhibition potently blocks LRRK2 release in exosomes, but familial mutations in LRRK2 had no effect on secretion. LRRK2 levels were overall comparable but highly variable in urinary exosomes derived from PD cases and age-matched controls, although very high LRRK2 levels were detected in some PD affected cases. We further characterized LRRK2 exosome release in neurons and macrophages in culture, and found that LRRK2-positive exosomes circulate in cerebral spinal fluid (CSF). Together, these results define a pathway for LRRK2 extracellular release, clarify one function of the LRRK2 14-3-3 interaction and provide a foundation for utilization of LRRK2 as a biomarker in clinical trial
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