Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Mol Genet Genomic Med. 2023 Jul;11(7):e2167. doi: 10.1002/mgg3.2167. Epub 2023 Mar 26.
The majority of genetic epilepsies remain unsolved in terms of specific genotype. Phenotype-based genomic analyses have shown potential to strengthen genomic analysis in various ways, including improving analytical efficacy.
We have tested a standardised phenotyping method termed 'Phenomodels' for integrating deep-phenotyping information with our in-house developed clinical whole exome/genome sequencing analytical pipeline. Phenomodels includes a user-friendly epilepsy phenotyping template and an objective measure for selecting which template terms to include in individualised Human Phenotype Ontology (HPO) gene panels. In a pilot study of 38 previously solved cases of developmental and epileptic encephalopathies, we compared the sensitivity and specificity of the individualised HPO gene panels with the clinical epilepsy gene panel.
The Phenomodels template showed high sensitivity for capturing relevant phenotypic information, where 37/38 individuals' HPO gene panels included the causative gene. The HPO gene panels also had far fewer variants to assess than the epilepsy gene panel.
We have demonstrated a viable approach for incorporating standardised phenotype information into clinical genomic analyses, which may enable more efficient analysis.
大多数遗传性癫痫在特定基因型方面仍未得到解决。基于表型的基因组分析已经显示出通过多种方式增强基因组分析的潜力，包括提高分析效果。
我们已经测试了一种称为“Phenomodels”的标准化表型方法，用于将深度表型信息与我们内部开发的临床全外显子/基因组测序分析管道相结合。Phenomodels 包括一个用户友好的癫痫表型模板和一种客观的方法，用于选择要包含在个体化人类表型本体 (HPO) 基因面板中的模板术语。在对 38 例先前已解决的发育性和癫痫性脑病病例的试点研究中，我们比较了个体化 HPO 基因面板与临床癫痫基因面板的敏感性和特异性。
Phenomodels 模板在捕获相关表型信息方面具有很高的敏感性，其中 37/38 个人的 HPO 基因面板包含了致病基因。HPO 基因面板需要评估的变体也比癫痫基因面板少得多。
我们已经证明了一种将标准化表型信息纳入临床基因组分析的可行方法，这可能使分析更有效率。
