Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK.
Department of Clinical Neurosciences, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
Epilepsia. 2021 Jun;62(6):1293-1305. doi: 10.1111/epi.16908. Epub 2021 May 5.
The clinical features of epilepsy determine how it is defined, which in turn guides management. Therefore, consideration of the fundamental clinical entities that comprise an epilepsy is essential in the study of causes, trajectories, and treatment responses. The Human Phenotype Ontology (HPO) is used widely in clinical and research genetics for concise communication and modeling of clinical features, allowing extracted data to be harmonized using logical inference. We sought to redesign the HPO seizure subontology to improve its consistency with current epileptological concepts, supporting the use of large clinical data sets in high-throughput clinical and research genomics.
We created a new HPO seizure subontology based on the 2017 International League Against Epilepsy (ILAE) Operational Classification of Seizure Types, and integrated concepts of status epilepticus, febrile, reflex, and neonatal seizures at different levels of detail. We compared the HPO seizure subontology prior to, and following, our revision, according to the information that could be inferred about the seizures of 791 individuals from three independent cohorts: 2 previously published and 150 newly recruited individuals. Each cohort's data were provided in a different format and harmonized using the two versions of the HPO.
The new seizure subontology increased the number of descriptive concepts for seizures 5-fold. The number of seizure descriptors that could be annotated to the cohort increased by 40% and the total amount of information about individuals' seizures increased by 38%. The most important qualitative difference was the relationship of focal to bilateral tonic-clonic seizure to generalized-onset and focal-onset seizures.
We have generated a detailed contemporary conceptual map for harmonization of clinical seizure data, implemented in the official 2020-12-07 HPO release and freely available at hpo.jax.org. This will help to overcome the phenotypic bottleneck in genomics, facilitate reuse of valuable data, and ultimately improve diagnostics and precision treatment of the epilepsies.
癫痫的临床特征决定了其定义方式，而这反过来又指导了治疗方法。因此，考虑构成癫痫的基本临床实体对于研究病因、病程和治疗反应至关重要。人类表型本体（HPO）在临床和研究遗传学中被广泛用于简明地交流和建模临床特征，允许使用逻辑推理来协调提取的数据。我们试图重新设计 HPO 发作子本体，以使其更符合当前的癫痫概念，支持在高通量临床和研究基因组学中使用大型临床数据集。
我们根据 2017 年国际抗癫痫联盟（ILAE）操作性发作类型分类创建了一个新的 HPO 发作子本体，并在不同的详细程度上整合了癫痫持续状态、热性、反射性和新生儿发作的概念。我们根据来自三个独立队列的 791 个人的发作信息，比较了修订前后的 HPO 发作子本体：两个之前发表的队列和 150 个新招募的队列。每个队列的数据都以不同的格式提供，并使用 HPO 的两个版本进行了协调。
新的发作子本体将发作的描述性概念数量增加了 5 倍。可以注释到队列中的发作描述符数量增加了 40%，个体发作信息的总量增加了 38%。最重要的定性差异是局灶性强直-阵挛发作与全面性和局灶性发作之间的关系。
我们生成了一个详细的当代概念映射，用于协调临床发作数据，已在官方 2020-12-07 HPO 版本中实现，并可在 hpo.jax.org 免费获取。这将有助于克服基因组学中的表型瓶颈，促进有价值数据的重复使用，并最终改善癫痫的诊断和精准治疗。
