BACKGROUND The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient's phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. RESULTS We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform, with remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex's main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex's broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards' recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters. Examining use-cases from a variety of TGex users world-wide, we demonstrate its high diagnostic yields (42% for single exome and 50% for trios in 1500 rare genetic disease cases) and critical actionable genetic findings. The platform's support for integration with EHR and LIMS through dedicated APIs facilitates automated retrieval of patient data for TGex's customizable reporting engine, establishing a rapid and cost-effective workflow for an entire range of clinical genetic testing, including rare disorders, cancer predisposition, tumor biopsies and health screening. CONCLUSIONS TGex is an innovative tool for the annotation, analysis and prioritization of coding and non-coding genomic variants. It provides access to an extensive knowledgebase of genomic annotations, with intuitive and flexible configuration options, allows quick adaptation, and addresses various workflow requirements. It thus simplifies and accelerates variant interpretation in clinical genetics workflows, with remarkable diagnostic yield, as exemplified in the described use cases. TGex is available at http://tgex.genecards.org/.

中文翻译：

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使用TGex进行基因组分析和知识驱动的变体解释。

背景技术临床遗传学革命带来了巨大的机遇，同时伴随着重大的挑战。临床遗传学的基本任务是分析基因组，并确定患者表型和症状所依据的最相关的遗传变异。全基因组测序的采用要求新颖的能力来解释非编码变体。结果我们介绍了TGex，转化基因组学专家，这是一个新颖的基因组变异分析和解释平台，具有出色的外显子组分析能力和开创性的非编码变异解释方法。TGex的主要优势是将最先进的变异过滤与我们高效的基因表型解释工具VarElect进行的知识驱动分析相结合。VarElect利用了广泛使用的GeneCards知识库，该知识库集成了来自> 150个自动挖掘的数据源的信息。访问如此全面的数据汇编还有助于TGex广泛的变体注释，支持证据探索和决策制定。TGex具有交互式，用户友好且易于调整的界面，符合ACMG，并具有自动报告系统。除了全面的完整外显子组序列功能外，TGex还涵盖了创新的非编码变体解释，以达到在临床遗传学实践中最大程度利用整个基因组序列分析的目标。GeneCards最近开发的GeneHancer可以实现这一点，GeneHancer是一种新型的，具有完整注释的人类增强子和启动子数据库。检查来自世界各地的各种TGex用户的用例，我们证明了其较高的诊断率（在1500种罕见遗传病病例中，单个外显子组的诊断率为42％，三重奏组的诊断率为50％）和关键的可行遗传结果。该平台支持通过专用API与EHR和LIMS集成，从而有助于自动检索TGex可定制报告引擎的患者数据，从而为整个临床基因测试（包括罕见疾病，癌症易感性，肿瘤活检）建立了快速且经济高效的工作流程和健康检查。结论TGex是一种创新工具，用于注释，分析和区分编码和非编码基因组变异的优先级。它提供了访问广泛的基因组注释知识库的途径，并具有直观而灵活的配置选项，可以快速进行调整，并满足各种工作流程要求。因此，它可以简化和加速临床遗传学工作流程中的变体解释，并具有明显的诊断结果，如在所描述的使用案例中所举例说明的那样。TGex可从http://tgex.genecards.org/获得。