Workflow for the implementation of precision genomics in healthcare. Precision genomics in healthcare

To enable the implementation of precise genomics in a local healthcare system, we devised a pipeline for filtering and reporting of relevant genetic information to healthy individuals based on exome or genome data. In our analytical pipeline, the first tier of filtering is variant-centric and it is based on the selection of annotated pathogenic, protective, risk factor and drug response variants, and their one-by-one detailed evaluation. This is followed by a second-tier gene-centric deconstruction and filtering of virtual gene lists associated with diseases, and VUS-centric filtering according to ACMG pathogenicity criteria and pre-defined deleteriousness criteria. By applying this filtering protocol, we were able to provide valuable insights regarding the carrier status, pharmacogenetic profile, actionable cardiovascular and cancer predispositions, and potentially pathogenic variants of unknown significance to our patients. Our experience demonstrates that genomic profiling can be implemented into routine healthcare and provide information of medical significance.

为实现在基层医疗系统中应用精准基因组学（precision genomics），我们开发了一套基于外显子组（exome）或全基因组（genome）数据，为健康个体筛选并报告相关遗传信息的分析流程。在本分析流程中，首轮筛选以变异为中心（variant-centric），基于已注释的致病（pathogenic）、保护（protective）、风险因子及药物反应相关变异开展筛选，并对上述变异逐一进行详细评估。随后开展第二轮筛选：先以基因为中心（gene-centric）对与疾病相关的虚拟基因列表进行解构与筛选，再依据美国医学遗传学与基因组学学会（ACMG, American College of Medical Genetics and Genomics）致病性判定标准及预先定义的有害性判定标准，开展以意义未明变异（VUS, Variant of Uncertain Significance）为中心的筛选。通过应用本筛选方案，我们可为患者提供关于携带者状态、药物基因组学（pharmacogenetic）特征谱、可干预的心血管疾病与癌症易感倾向，以及潜在致病性意义未明变异的宝贵临床参考。本研究的实践经验表明，基因组谱分析（genomic profiling）可融入常规医疗体系，并提供具有重要医学价值的信息。