An informatics approach to analyzing the incidentalome
An informatics approach to analyzing the incidentalome
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DOI：
10.1038/gim.2012.112
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发表时间：
2013-01-01
影响因子：
8.8
通讯作者：
Evans, James P.
中科院分区：
文献类型：
--
作者：
Berg, Jonathan S.;Adams, Michael;Evans, James P.
下一代测序已经改变了遗传研究，并有望彻底改变临床诊断。然而，大量的数据和不可避免的偶然发现需要新的分析方法。因此，我们首次实施了一种策略，该策略利用先验结构化框架和保守阈值来选择临床相关的偶然发现。方法：我们分类为2，016个与孟德尔疾病相关的基因根据临床实用性和有效性分成“箱”，并使用计算算法分析80个全基因组序列，以探索在模拟的真实的-世界设置。结果：该算法有效地减少了需要人工审查的变体数量，并识别了可能具有临床相关性的偶然变体。纳入人类基因突变数据库提高了错义突变的产量，但也揭示了相当大比例的所谓的致病突变是missible.Conclusion：这种方法是适应任何临床相关的bin结构，可扩展的临床实验室工作流程的需求，灵活的基因组学的进步。我们预计，这一策略的应用将促进预测试知情同意，实验室分析，并在临床背景下测试后返回的结果。遗传医学2013：15（1）：36-44
Purpose: Next-generation sequencing has transformed genetic research and is poised to revolutionize clinical diagnosis. However, the vast amount of data and inevitable discovery of incidental findings require novel analytic approaches. We therefore implemented for the first time a strategy that utilizes an a priori structured framework and a conservative threshold for selecting clinically relevant incidental findings.Methods: We categorized 2,016 genes linked with Mendelian diseases into "bins" based on clinical utility and validity and used a computational algorithm to analyze 80 whole-genome sequences in order to explore the use of such an approach in a simulated real-world setting.Results: The algorithm effectively reduced the number of variants requiring human review and identified incidental variants with likely clinical relevance. Incorporation of the Human Gene Mutation Database improved the yield for missense mutations but also revealed that a substantial proportion of purported disease-causing mutations were misleading.Conclusion: This approach is adaptable to any clinically relevant bin structure, scalable to the demands of a clinical laboratory work-flow, and flexible with respect to advances in genomics. We anticipate that application of this strategy will facilitate pretest informed consent, laboratory analysis, and posttest return of results in a clinical context. Genet Med 2013:15(1):36-44