实施乳腺癌综合基因组风险评估:从电子医疗记录和基因组学研究中吸取的教训
Cong Liu1,2, Katherine D Crew3, Jennifer Morse4
1Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, United States.
一个自动化管道,整合多基因风险评分 (PRS) 和其它因素,对1万多名女性进行乳腺癌风险评估是可行的. 该系统有效地识别高风险个体和遗传变异,克服运营挑战.
科学领域:
- 基因组学和精准医学精准医学
- 临床信息学 临床信息学
- 癌症流行病学 癌症流行病学
背景情况:
- 准确的乳腺癌风险评估对于早期发现和预防策略至关重要.
- 将多基因风险评分 (PRS) 与临床和家族史数据相结合,可以提供更全面的风险概况.
- 现有的风险模型在多机构数据协调和操作化方面经常面临挑战.
研究的目的:
- 开发和实施一个自动化的,多机构管道用于乳腺癌风险评估.
- 将多基因风险评分 (PRS),单基因变异,家族史和临床因素整合到统一的风险评分中.
- 识别和解决在不同临床场所部署此类系统的运营挑战.
主要方法:
- 实施了五个阶段的,涉及十个地点的多机构流程.
- 来自REDCap调查,PRS/单基报告和MeTree谱系的数据被规范化并通过CanRisk API的REDCap插件进行处理.
- 使用代测试,映射规则和数据归算策略来解决数据异质性和缺失信息.
主要成果:
- 该管道成功为超过10,000名妇女提供了综合风险评估.
- 评估的女性中有3.6%的人一生风险≥25%,0.9%的人携带致病变体.
- 自动化管道的风险评分与手动生成的评分有很强的一致性,验证了其准确性.
结论:
- 大规模的乳腺癌风险报告,与PRS集成,可以通过强大的互操作性标准实现.
- 成功实施取决于有效的跨平台数据协调和利益相关者的协调.
- 持续面临的挑战包括管理边界风险沟通和模型版本漂移.
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