Six questions on the construction of ontologies in biomedicine

(Report assembled for the Workshop of the AMIA Working Group on Formal Biomedical Knowledge Representation in connection with AMIA Symposium, Washington DC, 2005.) Best practices in ontology building for biomedicine have been frequently discussed in recent years. However there is a range of seemingly disparate views represented by experts in the field. These views not only reflect the different uses to which ontologies are put, but also the experiences and disciplinary background of these experts themselves. We asked six questions related to biomedical ontologies to what we believe is a representative sample of ontologists in the biomedical field and came to a number conclusions which we believe can help provide an insight into the practical problems which ontology builders face today

Perspectives on next steps in classification of oro-facial pain - part 1: role of ontology

The purpose of this study was to review existing principles of oro-facial pain classifications and to specify design recommendations for a new system that would reflect recent insights in biomedical classification systems, terminologies and ontologies. The study was initiated by a symposium organised by the International RDC/TMD Consortium Network in March 2013, to which the present authors contributed. The following areas are addressed: problems with current classification approaches, status of the ontological basis of pain disorders, insufficient diagnostic aids and biomarkers for pain disorders, exploratory nature of current pain terminology and classification systems, and problems with prevailing classification methods from an ontological perspective. Four recommendations for addressing these problems are as follows: (i) develop a hypothesis-driven classification structure built on principles that ensure to our best understanding an accurate description of the relations among all entities involved in oro-facial pain disorders; (ii) take into account the physiology and phenomenology of oro-facial pain disorders to adequately represent both domains including psychosocial entities in a classification system; (iii) plan at the beginning for field-testing at strategic development stages; and (iv) consider how the classification system will be implemented. Implications in relation to the specific domains of psychosocial factors and biomarkers for inclusion into an oro-facial pain classification system are described in two separate papers

Perspectives on next steps in classification of oro-facial pain - part 2: role of psychosocial factors

This study was initiated by a symposium, in which the present authors contributed, organised by the International RDC/TMD Consortium Network in March 2013. The purpose of the study was to review the status of biobehavioural research - both quantitative and qualitative - related to oro-facial pain (OFP) with respect to the aetiology, pathophysiology, diagnosis and management of OFP conditions, and how this information can optimally be used for developing a structured OFP classification system for research. In particular, we address representation of psychosocial entities in classification systems, use of qualitative research to identify and understand the full scope of psychosocial entities and their interaction, and the usage of classification system for guiding treatment. We then provide recommendations for addressing these problems, including how ontological principles can inform this process

The OBO Foundry: Coordinated Evolution of Ontologies to Support Biomedical Data Integration

The value of any kind of data is greatly enhanced when it exists in a form that allows it to be integrated with other data. One approach to integration is through the annotation of multiple bodies of data using common controlled vocabularies or ‘ontologies’. Unfortunately, the very success of this approach has led to a proliferation of ontologies, which itself creates obstacles to integration. The Open Biomedical Ontologies (OBO) consortium has set in train a strategy to overcome this problem. Existing OBO ontologies, including the Gene Ontology, are undergoing a process of coordinated reform, and new ontologies being created, on the basis of an evolving set of shared principles governing ontology development. The result is an expanding family of ontologies designed to be interoperable, logically well-formed, and to incorporate accurate representations of biological reality. We describe the OBO Foundry initiative, and provide guidelines for those who might wish to become involved in the future

Infectious Disease Ontology

Technological developments have resulted in tremendous increases in the volume and diversity of the data and information that must be processed in the course of biomedical and clinical research and practice. Researchers are at the same time under ever greater pressure to share data and to take steps to ensure that data resources are interoperable. The use of ontologies to annotate data has proven successful in supporting these goals and in providing new possibilities for the automated processing of data and information. In this chapter, we describe different types of vocabulary resources and emphasize those features of formal ontologies that make them most useful for computational applications. We describe current uses of ontologies and discuss future goals for ontology-based computing, focusing on its use in the field of infectious diseases. We review the largest and most widely used vocabulary resources relevant to the study of infectious diseases and conclude with a description of the Infectious Disease Ontology (IDO) suite of interoperable ontology modules that together cover the entire infectious disease domain

Opposite macrophage polarization in different subsets of ovarian cancer: observation from a pilot study

The role of the innate immune system in ovarian cancer is gaining importance. The relevance of tumor-associated macrophages (TAM) is insufficiently understood. In this pilot project, comprising the immunofluorescent staining of 30 biopsies taken from 24 patients with ovarian cancer, we evaluated the presence of total TAM (cluster of differentiation (CD) 68 expression), M1 (major histocompatibility complex (MHC) II expression), and M2 (anti-mannose receptor C type 1 (MRC1) expression), and the blood vessel diameter. We observed a high M1/M2 ratio in low-grade ovarian cancer compared to high-grade tumors, more total TAM and M2 in metastatic biopsies, and a further increase in total TAM and M2 at interval debulking, without beneficial effects of bevacizumab. The blood vessel diameter was indicative for M2 tumor infiltration (Spearman correlation coefficient of 0.65). These data mainly reveal an immune beneficial environment in low-grade ovarian cancer in contrast to high-grade serous ovarian cancer, where immune suppression is not altered by neoadjuvant therapy

The P2X7 receptor contributes to seizures and inflammation-driven long-lasting brain hyperexcitability following hypoxia in neonatal mice.

Neonatal seizures represent a clinical emergency. However, current anti-seizure medications fail to resolve seizures in ~50% of infants. The P2X7 receptor (P2X7R) is an important driver of inflammation, and evidence suggests that P2X7R contributes to seizures and epilepsy in adults. However, no genetic proof has yet been provided to determine what contribution P2X7R makes to neonatal seizures, its effects on inflammatory signalling during neonatal seizures, and the therapeutic potential of P2X7R-based treatments on long-lasting brain excitability. Neonatal seizures were induced by global hypoxia in 7-day-old mouse pups (P7). The role of P2X7Rs during seizures was analysed in P2X7R-overexpressing and knockout mice. Treatment of wild-type mice after hypoxia with the P2X7R antagonist JNJ-47965567 was used to determine the effects of the P2X7R on long-lasting brain hyperexcitability. Cell type-specific P2X7R expression was analysed in P2X7R-EGFP reporter mice. RNA sequencing was used to monitor P2X7R-dependent hippocampal downstream signalling. P2X7R deletion reduced seizure severity, whereas P2X7R overexpression exacerbated seizure severity and reduced responsiveness to anti-seizure medication. P2X7R deficiency led to an anti-inflammatory phenotype in microglia, and treatment of mice with a P2X7R antagonist reduced long-lasting brain hyperexcitability. RNA sequencing identified several pathways altered in P2X7R knockout mice after neonatal hypoxia, including a down-regulation of genes implicated in inflammation and glutamatergic signalling. Treatments based on targeting the P2X7R may represent a novel therapeutic strategy for neonatal seizures with P2X7Rs contributing to the generation of neonatal seizures, driving inflammatory processes and long-term hyperexcitability states