The Human Phenotype Ontology: Accelerating Computational Integration of Clinical Data for Genomics

项目摘要/摘要 为了提高对罕见疾病的诊断效率，我们在2008年开发了人类表型本体(HPO)，作为 提供表型异常标准化术语的综合生物信息资源 用于分析人类疾病。HPO减少了疾病描述中的歧义，从而实现了更强大的 鉴别诊断和临床护理-并实现基因组数据的表型上下文 诊断学和精准医学。 具有HPO项的微分诊断的计算算法的性能关键取决于 疾病HPO注解的全面性和深刻性。然而，目前我们的手动性质 生物修复过程限制了这些注释的质量、深度和覆盖面。因此，这项提案 目标是通过自动执行部分 管理和扩展计算疾病模型。 这个项目，HPO：加速基因组学临床数据的计算集成，将维护和 预留卫生保健署资源，以满足越来越多采用 HPO。我们将通过以下方式实现这一目标：1)自动化HPO开发、维护和发布流程；2) 开发罕见疾病治疗和干预的代表，以及3)扩展我们目前的 计算疾病模型，以表示时间进程、性别偏见和事件频率，并将 案例报告数据。我们还为社区贡献提供可持续的解决方案，提供用户友好的网络- 基于门户，使贡献者能够审查本体和注释并提出改进建议，以及 发展HPO贡献者社区。 总而言之，我们的项目满足了推进卫生保健目标的最迫切需要，以确保可持续、 强大而严谨的开发，使HPO资源能够支持新社区、新应用和 更多的医学学科。

PROJECT SUMMARY/ABSTRACT To improve diagnostic yield for rare diseases, we developed the Human Phenotype Ontology (HPO) in 2008 as a comprehensive bioinformatic resource that provides a standardized terminology of phenotypic abnormalities for the analysis of human diseases. HPO reduces ambiguity in disease descriptions—thus enabling more robust differential diagnosis and clinical care—and enables phenotypic contextualization of genomic data for diagnostics and precision medicine. The performance of computational algorithms for differential diagnostics with HPO terms depends critically on the comprehensiveness and depth of HPO annotations for diseases. However, the current manual nature of our biocuration process has limited the quality, depth, and coverage of these annotations. Therefore, this proposal's objectives are to greatly expand the corpus of disease-phenotype annotations by automating portions of the curation and expanding the computational disease model. This project, HPO: Accelerating Computational Integration of Clinical Data for Genomics, will maintain and advance HPO resources to address the needs of a growing number of medical disciplines that have adopted the HPO. We will achieve this goal by 1) automating HPO development, maintenance, and release processes, 2) developing representations of rare disease treatments and interventions, and 3) extending our current computational disease models to represent time course, sex biases, and frequency of events, and to incorporate case report data. We also provide a sustainable solution to community contribution with a user-friendly, web- based portal to enable contributors to vet and suggest improvements to the ontology and the annotations and grow the HPO contributor community. In summary, our project addresses the most pressing needs for advancements of the HPO to ensure sustainable, robust, and rigorous development, to enable HPO resources to support new communities, new applications, and more medical disciplines.