Beyond medically actionable results: an analytical pipeline for decreasing the burden of returning all clinically significant secondary findings
Beyond medically actionable results: an analytical pipeline for decreasing the burden of returning all clinically significant secondary findings
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DOI：
10.1007/s00439-020-02220-9
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发表时间：
2020-09-06
期刊：
影响因子：
5.3
通讯作者：
Bombard, Yvonne
中科院分区：
文献类型：
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作者：
Reble, Emma;Gutierrez Salazar, Mariana;Bombard, Yvonne
基因组测序的进步增加了识别二次发现(SFS)的可能性。目前的指南建议分析59个医学上可操作的基因；然而，患者的偏好表明有兴趣了解更广泛的SFS群体。我们的目标是开发一种分析管道，用于有效分析和返回所有具有临床意义的SFS。我们开发了一个流水线，包括五个SFS类别的全面基因列表和筛选参数，以确定每个类别的变体的优先顺序。我们将该管道应用于42个外显子，以评估其可行性和有效性。对每一类具有临床意义的SF基因进行了全面的筛选：(1)90个医学上可操作的基因和28个药物基因组变异；(2)17个常见疾病风险变异；(3)3166个孟德尔病基因；(4)7个早发性神经退行性疾病基因；(5)688个携带者状态结果。使用我们的流水线对42个外显子进行分析，与原始分析(13,036.56+/-59.72个原始变异体/外显子组比161.32+/-7.68个过滤变异体/外显子组)相比，变异体显著减少(>；98%)，并有助于整个分析过程的时间和成本节约。我们的流程代表着在克服与返回所有临床相关的SFS以允许其在临床实践中常规实施相关的分析挑战方面迈出的关键一步。
Genomic sequencing advances have increased the potential to identify secondary findings (SFs). Current guidelines recommend the analysis of 59 medically actionable genes; however, patient preferences indicate interest in learning a broader group of SFs. We aimed to develop an analytical pipeline for the efficient analysis and return of all clinically significant SFs. We developed a pipeline consisting of comprehensive gene lists for five categories of SFs and filtration parameters for prioritization of variants in each category. We applied the pipeline to 42 exomes to assess feasibility and efficiency. Comprehensive lists of clinically significant SF genes were curated for each category: (1) 90 medically actionable genes and 28 pharmacogenomic variants; (2) 17 common disease risk variants; (3) 3166 Mendelian disease genes, (4) 7 early onset neurodegenerative disorder genes; (5) 688 carrier status results. Analysis of 42 exomes using our pipeline resulted in a significant decrease (> 98%) in variants compared to the raw analysis (13,036.56 +/- 59.72 raw variants/exome vs 161.32 +/- 7.68 filtered variants/exome), and aided in time and costs savings for the overall analysis process. Our pipeline represents a critical step in overcoming the analytic challenge associated with returning all clinically relevant SFs to allow for its routine implementation in clinical practice.