The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

The Human Phenotype Ontology (HPO)—a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases—is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO’s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.

No abstract

BackgroundNegative attitudes towards patients with borderline personality disorder (BPD) may affect their treatment. We aimed to identify attitudes toward patients with BPD.MethodsClinicians in four psychiatric hospitals in Israel (n = 710; psychiatrists, psychologists, social workers and nurses) were approached and completed questionnaires on attitudes toward these patients.ResultsNurses and psychiatrists reported encountering a higher number of patients with BPD during the last month, and exhibited more negative attitudes and less empathy toward these patients than the other two professions. The whole sample evaluated the decision to hospitalize such a patient as less justified than the decision to hospitalize a patient with Major Depressive Disorder. Negative attitudes were positively correlated with caring for greater numbers of patients with BPD in the past month and in the past 12 months. Nurses expressed the highest interest in studying short-term methods for treating patients with BPD and a lower percentage of psychiatrists expressed an interest in improving their professional skills in treating these patients.ConclusionsThe findings show that nurses and psychiatrists differ from the other professions in their experience and attitudes toward patients with BPD. We conclude that nurses and psychiatrists may be the target of future studies on their attitudes toward provocative behavioral patterns (e.g., suicide attempts) characterizing these patients. We also recommend implementing workshops for improving staff attitudes toward patients with BPD.

1. Microcultures were grown containing small numbers of hippocampal neurons. The neurons grew on glial cells attached to patches of either collagen or palladium. A layer of agarose underlying the microcultures prevented connections from forming between nearby microcultures. 2. Neurons formed strong chemical synaptic connections within each microculture, with monosynaptic fast-excitatory, fast-inhibitory, and slow-inhibitory synaptic actions. 3. Small networks with as few as two neurons generated epileptiform activity that closely resembled the epileptiform activity seen in mass cultures containing thousands of neurons. The epileptiform activity was observed when microcultures that were grown for weeks in blockers of synaptic activity (kynurenate and elevated Mg2+) were washed free of these blockers. 4. Such a microculture technique allows study of epileptiform activity in a simplified system and facilitates analysis of the synaptic actions underlying the epileptiform activity.

We examined the vulnerability to excitotoxicity of rat oligodendrocytes in dissociated cell culture at different developmental stages. Mature oligodendrocytes that express myelin basic protein were resistant to excitotoxic injury produced by kainate, whereas earlier stages in the oligodendrocyte lineage were vulnerable to this insult. To test the hypothesis that the sensitivity of immature oligodendrocytes and the resistance of mature oligodendrocytes to kainate toxicity were due to differences in membrane responsiveness to kainate, we used whole-cell patch-clamp recording. Oligodendrocyte precursors in cultures vulnerable to kainate toxicity responded to 500 microM kainate with large inward currents, whereas mature myelin basic protein-expressing oligodendrocytes in cultures resistant to kainate toxicity showed no clear response to application of this agonist. We assayed expression of glutamate receptor subunits (GluR) -2, -4, -6, -7, and KA2 using immunoblot analysis and found that expression of all of these glutamate receptors was significantly down-regulated in mature oligodendrocytes. These results suggest a striking developmental regulation of glutamate receptors in oligodendrocytes and suggest that the vulnerability of oligodendrocytes to non- N-methyl-D-aspartate receptor-mediated excitotoxicity might be much greater in developing oligodendrocytes than after the completion of myelination.

No abstract