MorbidGenes-Panel-v2022-02.1

<strong>Background</strong>: Identifying clinically relevant genetic variants is crucial for a fast and reliable genetic diagnosis. With exome sequencing now standard, diagnostic labs are in need of a, in principle, to-the-day-accurate list of genes associated with rare diseases. Manual curation efforts are slow and often disease specific, while efforts relying on single sources are too inaccurate and result in too many false-positive genes. <strong>Methods</strong>: We established the MorbidGenes panel based on a list of publicly available databases: OMIM, PanelApp, SysNDD, ClinVar, HGMD and GenCC. A simple logic allows inclusion of genes with sufficient evidence based on a voting algorithm. By providing an API endpoint, users can directly access the list and meta data for all relevant information on their genes of interest. <strong>Results</strong>: The panel currently includes 4,677 genes (v.2022-02.1, as of February 2022) with minimally sufficient evidence on disease causality to classify them as diagnostically relevant. Reproducible filtering and versioning allow the integration into diagnostic pipelines. In-house Implementation successfully removed false positive genes and reduced time requirements in routine exome diagnostics. The panel is updated monthly, and we will integrate novel sources on a regular basis. <strong>Conclusion</strong>: The MorbidGenes panel is a comprehensive and open overview of clinically relevant genes based on a growing list of sources. It supports genetic diagnostics labs by providing diagnostically relevant genes in a QM conform format on a monthly basis with more frequent updates planned. Once genomes are standard, diagnostically relevant non-coding regions will also be included.<strong>研究背景</strong>：精准识别临床相关遗传变异，是实现快速可靠的遗传诊断的核心前提。随着外显子组测序（exome sequencing）现已成为常规检测手段，遗传诊断实验室亟需一份原则上可实时更新且精准无误的罕见病关联基因清单。人工基因注释工作不仅效率低下，且通常仅针对单一疾病；而仅依赖单一数据源的注释方案准确性欠佳，易产生大量假阳性基因。 <strong>研究方法</strong>：本研究基于OMIM、PanelApp、SysNDD、ClinVar、HGMD及GenCC等公开数据库，构建了MorbidGenes基因面板（MorbidGenes panel）。本研究采用基于投票算法的简单逻辑规则，筛选具备充分证据的基因。通过开放API接口，用户可直接获取目标基因的完整清单及元数据信息。 <strong>研究结果</strong>：截至2022年2月，该基因面板（v.2022-02.1）目前共收录4677个基因，这些基因均具备最低限度的疾病因果关联证据，可归类为临床诊断相关基因。该面板具备可复现的筛选机制与版本化管理能力，可无缝集成至临床诊断工作流中。内部测试应用结果显示，该面板成功剔除了假阳性基因，并缩短了常规外显子组测序诊断的耗时。该面板每月更新一次，且我们将定期集成新的数据源。 <strong>研究结论</strong>：MorbidGenes基因面板是基于不断扩充的数据源构建的临床相关基因的全面开放汇总资源。该面板以符合质量管理（QM，Quality Management）规范的格式每月为遗传诊断实验室提供临床相关基因清单，并计划推出更频繁的更新方案，为实验室提供支持。当全基因组测序成为常规检测手段后，本面板还将纳入临床诊断相关的非编码区域序列信息。