講演情報
[O4-2]ゲノム情報の臨床的解釈を促進するVirtual Gene Panelの構築手法提案
○藤原 豊史1, 申 在紋1, 才津 浩智2, 山口 敦子3 (1.情報・システム研究機構 ライフサイエンス統合データベースセンター, 2.浜松医科大学 医学部 医化学講座, 3.東京都市大学 総合理工学研究科情報専攻)
Recently, virtual gene panels (VGPs), sets of causal genes associated with rare genetic diseases, have been used for the interpretation of the results of whole-genome sequencing (WGS). In the UK 100,000 Genomes Project pilot study on rare disease diagnosis, PanelApp which is a database containing 332 VGPs has been applied for automated variant filtering to accelerate the time-consuming interpretation process of WGS results and improve diagnostic rates. However, the design of these VGPs is a laborious task because they are curated manually. In this study, we implemented the new method in PubCaseFinder (https://pubcasefinder.dbcls.jp), a clinical decision support system, to automatically design VGPs and evaluated the potential of this method. To implement the method, we used the Mondo disease ontology (Mondo) and publicly available curated disease-gene associations in the MedGen, GenCC, and Orphadata databases. Mondo is a controlled vocabulary that integrates existing sources of disease definitions, such as OMIM and Orphanet. It provides a hierarchical structure that can be used for classification or “rolling up” diseases to higher-level groupings. Using this feature, any VGPs can be created by grouping diseases at any hierarchy of about 25,000 diseases included in Mondo and grouping the causal genes related to those diseases. In this presentation, we report the details of the VGP design method implemented on PubCaseFinder and the results of this study that showed our proposed method contributed to improving the time-consuming interpretation process of WGS results.