Assessment of a Highly Curated Somatic Oncology Database to Aid in the Interpretation of Clinically Important Variants in Next-Generation Sequencing Results
Assessment of a Highly Curated Somatic Oncology Database to Aid in the Interpretation of Clinically Important Variants in Next-Generation Sequencing Results
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DOI：
10.1016/j.jmoldx.2020.08.004
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发表时间：
2020-11-01
影响因子：
4.1
通讯作者：
Schmid, Maximilian
中科院分区：
文献类型：
--
作者：
Yaung, Stephanie J.;Krishna, Shuba;Schmid, Maximilian
本研究评估了NAVIFY Mutation Profiler的准确性，NAVIFY Mutation Profiler是一种基于云的CE-IVD软件，有助于解释在体细胞肿瘤学下一代测序检测中检测到的临床相关变异。该工具报告了基于不同水平的临床证据的分层分类，这些证据来自一个高度策划的、定期更新的数据库，该数据库来自医疗指南、药物批准和同行评审文献。对37例接受化疗（n = 10）、EGFR酪氨酸激酶抑制剂（TKI）（n = 5）或ALK TKI（n = 22）治疗的肺癌病例的下一代测序结果进行了回顾性分析。评估了几个方面，包括与人工策展相比的解释准确性，随着时间的推移策展内容更新的有效性，以及与公共数据库的一致性。对于没有靶向生物标志物的化疗病例，NAVIFY Mutation Profiler未发现任何靶向治疗。在EGFR和ALK TKI病例中，该软件将适当的靶向治疗与准确解释的含有耐药变异体的变异体组合相关联。在9种导致克唑替尼耐药的独特ALK突变中，NAVIFY Mutation Profiler为所有突变提供了正确注释，而OncoKB和癌症体细胞突变目录表明9种突变中有8种对克唑替尼耐药。对于分析的145种变体，NAVIFY Mutation Profiler和OncoKB显示出对可操作突变进行分类的基本一致性（Cohen kappa = 0.62）。此外，NAVIFY Mutation Profiler提供了不同地区的准确靶向治疗，并与不断发展的地区批准和医疗指南保持同步。
This study evaluated the accuracy of NAVIFY Mutation Profiler, a cloud-based CE-IVD software that aids in interpreting clinically relevant variants detected in somatic oncology next-generation sequencing tests. This tool reports tiered classifications based on different levels of clinical evidence from a highly curated, regularly updated database derived from medical guidelines, drug approvals, and peer-reviewed literature. A retrospective analysis was performed on next-generation sequencing results from 37 lung cancer cases treated with chemotherapy (n = 10), EGFR tyrosine kinase inhibitor (TKI) (n = 5), or ALK TKI (n = 22). Several aspects were assessed, including accuracy of interpretation compared with manual curation, validity of curation content updates over time, and agreement with public databases. For chemotherapy cases with no targetable biomarkers, NAVIFY Mutation Profiler did not identify any targeted therapies. In EGFR and ALK TKI cases, the software associated appropriate targeted therapies and accurately interpreted variant combinations containing drug-resistance variants. Of the nine unique ALK mutations conferring resistance to crizotinib, NAVIFY Mutation Profiler provided correct annotation for all mutations, whereas OncoKB and Catalogue of Somatic Mutations in Cancer indicated crizotinib resistance for eight of nine mutations. For 145 variants analyzed, NAVIFY Mutation Profiler and OncoKB showed substantial agreement (Cohen kappa = 0.62) for classifying actionable mutations. Furthermore, NAVIFY Mutation Profiler presented accurate targeted therapies across different regions and remained up-to-date with evolving regional approvals and medical guidelines.