Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.

中文翻译：

---

癌症体细胞基因组变异临床解释的统一元知识库。

精准肿瘤学依赖于对基因组变异的准确发现和解释，从而实现个体化诊断、预后和治疗选择。我们发现六个突出的体细胞癌变异知识库在内容、结构和支持的原始文献方面高度不同，在评估变异及其在临床环境中的相关性时阻碍了共识。我们开发了一个用于协调变体解释的框架，以生成包含 12,856 个汇总解释的元知识库。由于这种协调，我们展示了跨变体、疾病和药物的资源重叠方面的巨大收益。我们随后证明了患者队列和潜在临床意义的协调解释之间的匹配改进，观察到从每个知识库的平均 33% 增加到总体的 57%。我们的分析阐明了对变异解释数据开放、可互操作共享的需求。我们还提供了一个免费的网络界面 (search.cancervariants.org)，用于探索这六个知识库的统一解释。