Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
JCO Clin Cancer Inform. 2022 Feb;6:e2100144. doi: 10.1200/CCI.21.00144.
Interpretation of genomic variants in tumor samples still presents a challenge in research and the clinical setting. A major issue is that information for variant interpretation is fragmented across disparate databases, and aggregation of information from these requires building extensive infrastructure. To this end, we have developed Genome Nexus, a one-stop shop for variant annotation with a user-friendly interface for cancer researchers and clinicians.
Genome Nexus (1) aggregates variant information from sources that are relevant to cancer research and clinical applications, (2) allows high-performance programmatic access to the aggregated data via a unified application programming interface, (3) provides a reference page for individual cancer variants, (4) provides user-friendly tools for annotating variants in patients, and (5) is freely available under an open source license and can be installed in a private cloud or local environment and integrated with local institutional resources.
Genome Nexus is available at https://www.genomenexus.org. It displays annotations from more than a dozen resources including those that provide variant effect information (variant effect predictor), protein sequence annotation (Uniprot, Pfam, and dbPTM), functional consequence prediction (Polyphen-2, Mutation Assessor, and SIFT), population prevalences (gnomAD, dbSNP, and ExAC), cancer population prevalences (Cancer hotspots and SignalDB), and clinical actionability (OncoKB, CIViC, and ClinVar). We describe several use cases that demonstrate the utility of Genome Nexus to clinicians, researchers, and bioinformaticians. We cover single-variant annotation, cohort analysis, and programmatic use of the application programming interface. Genome Nexus is unique in providing a user-friendly interface specific to cancer that allows high-performance annotation of any variant including unknown ones.
Interpretation of cancer genomic variants is improved tremendously by having an integrated resource for annotations. Genome Nexus is freely available under an open source license.
在研究和临床环境中，肿瘤样本中基因组变异的解释仍然是一个挑战。一个主要问题是，变异解释的信息分散在不同的数据库中，从这些数据库中汇总信息需要建立广泛的基础设施。为此，我们开发了 Genome Nexus，这是一个用于变异注释的一站式服务，为癌症研究人员和临床医生提供了用户友好的界面。
Genome Nexus（1）从与癌症研究和临床应用相关的来源聚合变异信息，（2）允许通过统一的应用程序编程接口对聚合数据进行高性能的程序访问，（3）为每个癌症变异提供参考页面，（4）为患者注释变异提供用户友好的工具，（5）在开源许可证下免费提供，可以安装在私有云或本地环境中，并与本地机构资源集成。
Genome Nexus 可在 https://www.genomenexus.org 上获得。它显示了来自十多个资源的注释，包括提供变异效应信息的资源（变异效应预测器）、蛋白质序列注释（Uniprot、Pfam 和 dbPTM）、功能后果预测（Polyphen-2、Mutation Assessor 和 SIFT）、群体流行率（gnomAD、dbSNP 和 ExAC）、癌症群体流行率（Cancer hotspots 和 SignalDB）和临床可操作性（OncoKB、CIViC 和 ClinVar）。我们描述了几个用例，展示了 Genome Nexus 对临床医生、研究人员和生物信息学家的实用性。我们涵盖了单变异注释、队列分析和应用程序编程接口的程序使用。Genome Nexus 的独特之处在于提供了一个针对癌症的用户友好界面，允许对包括未知变异在内的任何变异进行高性能注释。
通过提供注释的综合资源，癌症基因组变异的解释得到了极大的改善。Genome Nexus 在开源许可证下免费提供。
